Effects of Electroacupuncture on Neural Function and Expression of Inflammation-Related Proteins NLRP3/Caspase-1 in Rats with Ischemic Stroke

Effects of Electroacupuncture on Neural Function and Expression of Inflammation-Related Proteins NLRP3/Caspase-1 in Rats with Ischemic Stroke | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Electroacupuncture on Neural Function and Expression of Inflammation-Related Proteins NLRP3/Caspase-1 in Rats with Ischemic Stroke Jian Wang, Yujiang Xi, ZhiFeng Wang, LiWei Xing, kun Zhang, Xiaoyu Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3791862/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective :To investigate the neuroprotective effects of electroacupuncture at Baihui and Dazhui on rats in an ischemia-reperfusion injury model. Methods: Forty-eight SPF male SD rats were randomly divided into sham operation group, model group, EA group and inhibitor group, with 12 rats in each group, and the middle cerebral arteryOcclusion (MCAO) model was established using the wire embolization method, and the model was successfully replicated and treated by acupuncture at Baihui and Dazhui. The neurological function scores were evaluated by Zea Longa neurological deficit score on days 1, 7 and 14 after treatment, and the volume of cerebral infarction was measured by 2, 3, 5-triphenyltetrazolium chloride staining. Detection of nod-like receptor protein 3 (NLRP3) and GSDMD gene expression by real-time fluorescence quantitative PCR , Western blot detection of NLRP3, GSDMD, Caspase-1 and other protein expression levels in rat brain tissue , and microglia levels were observed by immunofluorescence staining; the expression levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked adsorption assay. Results: Compared with the model group, the rats in the electroacupuncture group had significantly lower neurological deficit score ( p < 0.05), significantly reduced brain infarct volume ( p < 0.05), significantly reduced NLRP3 and GSDMD gene expression ( p < 0.05), reduced NLRP3, GSDMD, Caspase-1 and other protein expression water, IL-1β, IL-18 inflammatory factor expression were significantly reduced ( p < 0.05). Conclusion : Electroacupuncture can improve the symptoms of neurological injury in rats with ischemic stroke model, and may play a neuroprotective role by inhibiting NLRP3/Caspase-1 inflammatory pathway and reducing the expression of cell scorch-related proteins. Ischemic stroke Neuroinflammation Electroacupuncture NLRP3 Caspase-1 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 1. Introduction Ischemic stroke is a potentially fatal cerebrovascular condition defined by a sudden decrease in blood supply to specific brain parts. It is the leading cause of permanent disability and the second largest cause of mortality worldwide. Around 14 million people suffer from strokes each year globally [ 1 ]. Inflammatory response, autophagy, oxidative stress, and apoptosis are now widely acknowledged as being critical pathogenic pathways in the development of ischemic stroke[ 2 ]. Numerous ischemic cascade events follow an ischemic stroke, with neuroinflammatory damage playing a significant role in the injury process. Anti-inflammatory therapy might treat ischemic stroke as a novel therapeutic option. Numerous studies have demonstrated that activation of multiprotein complexes—inflammasomal NLRP3 plays a crucial role in metabolic disorders and various diseases including gout, heart disease, autoimmune diseases, and stroke[ 3 ]. Currently, anticoagulation, antiplatelet aggregation, thrombolysis, neuroprotective medicines, and vasodilator medications are utilized to treat ischemic stroke. These medications have some efficacy but are time-dependent and have certain negative effects[ 4 – 5 ]. Electroacupuncture therapy is gaining popularity as more and more clinical trials show it to be safe and efficient in treating ischemic cerebral infarction[ 6 ]. Following an ischemic stroke, a series of events known as the "ischemia cascade" raise the levels of pro-inflammatory mediators including IL-18 and IL-1, which damage healthy neurons and exacerbate the initial ischemic damage. Noticeably, NLRP3 can play a crucial role in coordinating host physiology and shaping central and peripheral immune/inflammatory responses through the release of IL-18, and IL-1β. Additionally, numerous investigations have demonstrated that NLRP3 activation is essential for ischemic stroke injury[ 7 ]. On the basis of previous research, this study investigated the possible mechanism of electroacupuncture in reducing nerve injury in ischemic stroke utilizing NLRP3/caspase-1 inflammatory pathway. 2. Materials and methods 2.1 Animals Forty-eight SPF male SD rats, weighing 220±10g, were provided by the Experimental Animal Center at Kunming Medical University. The experimental animal center at Kunming Medical University is where all of the animals were raised, and their qualification certificate number was SCXK (Dian) K2020-0015. The feeding temperature was set at 23 2°C with a 60% humidity level and a 12-hour light-dark cycle. The usual feed was given, with free access to food and drink. Each group of 12 rats was randomly divided into four groups: sham operation group, model operation group, electroacupuncture group and inhibitor group. The animals in this experiment were disposed of according to the 2006 Guideline of the Chinese Ministry of Science and Technology for the Care and Use of Laboratory Animals. 2.2 Reagents and instruments The reagents and instruments used in this research included a digital medical image analysis system (MOTIC Asia Optical Technology Co,Ltd), an electroacupuncture equipment (HANS-200A, Jisheng Medical instrument Co, Ltd,Nanjing,China), stainless disposable acupuncture needles (Hwato,0.18mm×13mm, Suzhou Medical Equipment Factory, Suzhou, China), Alexa Fluor ® 488Donkey Anti-Rabbit IgG Antibody (Invitrogen Reagent Corporation, Carlsbad,United States), Bicinchoninic acid protein quantification test kit (Beyotime Institute of Biotechnology,Jiangsu, China), primary antibody diluent for WB (GTX28208) (Beyotime Institute of Biotechnology, Jiangsu, China), Anti-Bax Monoclonal,Anti-BCL2 Polyclonal Antibody, Anti-Cleaved-caspase-3 (Asp175) antibody ( Biotechnology Santa Cruz Co, Ltd, Texas, United States), ammonium persulfate (MYM Biological Technology Company Limited, Chicago, IL, USA), polyvinylidene fluoride membrane (Invitrogen Reagent Corporation, Carlsbad, United States),In Situ Cell Apoptosis TUNEL Detection kit, (Hoffmann-La Roche Co, Ltd), and Reagent for glycine,56-40-6(Biosharp Biotechnology life science Co, Ltd, Anhui, China), 30% acrylamide and BIO-BEST 300M gel imaging analysis system (Solarbia Science and Biotechnology Co, Ltd, Beijing, China), Ultra High Sensitivity ECL chemiluminescence kit, batch number:50018 (Beyotime Institute of Biotechnology, Jiangsu, China). 2.3 Ischemic stroke model For the model group and electroacupuncture group, an ischemic stroke model was created and detailed elsewhere. The following were the detailed procedures: after anesthesia, 3.5 percent pentobarbital sodium was administered intraperitoneally, and a neck incision was operated with tissue separated layer by layer. The external carotid artery (ECA), the internal carotid artery (ICA), and the left common carotid artery (CCA) were all exposed and then separated. The ECA is bundled and separated, as w well as its branches. After making a small cut at the beginning of the ECA residual, a smooth suture embolization was placed into the intracranial section of the intracranial segment of the ICA. The suture embolus was inserted at a depth of approximately 18 ± 0.5 cm from the carotid bifurcation. The blood supply to the internal carotid artery and middle cerebral artery can be restored by returning the bulb of the external carotid artery to the external carotid artery during perfusion and by embolization via the external suture. After ensuring correct postoperative surgery and observing for abnormalities, the skin was sutured and the animals were placed back in their cages. Insulation feeding was given, as well as observation. Animals were examined for ischemia within the time limit to exclude animals with intact limbs or those that had died. In the sham-operated group, only the left common carotid artery was isolated and no other treatment was performed. The suture embolization was removed one and a half hours after surgery, and no thrombus or bleeding was seen in the ICA, indicating successful reperfusion. 2.4 Intervention methods The electroacupuncture group: after modeling, an electroacupuncture intervention was performed on day 1. Acupoint selection was done according to Hua Xingbang et al "Development of Rat Acupoint Sites.". BaiHui (DU20)" (middle of parietal bone of rats) and "DaiZhui (DU14)" (in the depression of the seventh cervical spine's subspinal process in the prone position on the posterior median line)[13]. Among them, acupuncture was performed at "Baihui" point about 2mm in a percutaneous oblique direction to the forehead along the median line of the brain, and at "Dazhui" point directly for 5mm. After the needling, Hans-200 electroacupuncture instrument was used to select density wave with a frequency of 2Hz/100Hz and an intensity of 1mA. The needles were left in place for 30 minutes, and then electro-acupuncture was utilized once a day for two weeks, after which the procedure was repeated. To avoid upsetting the rats, the entire treatment was carried out quickly, gently, and smoothly. No interventions were given to either the model control group or the sham operation group. 2.5 Methods of indicator detection 2.5.1 Neurological deficit score.Zea Longa's 5-point scoring method was used to evaluate the degree of neurological deficit in rats. The neurological deficit score was 0, with no obvious defect; 1 point, the right forepaw was not fully extended; 2 points, turning to the opposite side; 3 points, fall to the opposite side; 4 points, no spontaneous walking or loss of consciousness. 2.5.2 TTC staining. After the neurological deficit score was completed, 6 rats in each group were randomly selected and sacrificed under anesthesia for brain tissue harvesting. TTC staining was used to stain the meningeal sections, and the stained brain slices of rats in each group were photographed using a digital camera. Image Pro-Plus(Version 6.0) software was used to investigate and calculate the infarct size, and the infarct size was calculated by the investigator. The formula was as follows: percentage of infarction (percentage)=[pale area mass /(pale area mass + non-pale area mass)]×100%. 2.5.3 Nissl staining. After conventional dewaxing and hydration, paraffin sections were immersed in tar purple staining solution, baked at 56°C for 1h, and immersed in 0.5% hydrochloric acid ethanol fractionation solution for 4-20s. After dehydration, the sections were sealed with neutral gel and stored away from light. A 400-fold light microscope was used to investigate the morphological and structural alterations in the rat brain. 2.5.4 Western blot. With 200 microliter of RIPA lysate (containing protease inhibitor), 80 mg of damaged brain tissue was homogenized. The entire protein in each rat's brain tissue was extracted. BCA was used to calculate the sample protein concentration, and denaturation was done in a metal bath at 95°C for 10 minutes. Sample loading, electrophoresis, membrane transfer, blocking with 5% skim milk powder for 2 hours, overnight at 4 °C, primary antibody incubation against caspase-1, NLRP3, and microtubulin (1SDS-PAGE 3000), membrane washing, and secondary antibody incubation (sheep anti-mouse IgG 1:10 00 and sheep anti-rabbit IgG 1:10 00). ecl hypersensitive Chemiluminescent solutions were uniformly distributed and photographed using an ECL imaging system. Image Pro Plus software was used to assess the gray value of each target protein/β-tubulin, and the gray value of the strips was used to detect the relative expression intensity of the target protein. 2.5.5 Real-time fluorescent quantitative PCR.RNA was extracted from the brain tissue of each group, and cDNA was synthesized according to the reverse transcription kit. The cDNA was used as a template for PCR reaction on a fluorescence quantitative PCR instrument. Primers were synthesized by Guangzhou Ruibo Biological Co., LTD. See Table 1 for details. Total RNA was extracted with Trizol reagent, 1μg of total RNA was reverse transcribed with a reverse transcription kit, and 2μl of first-strand cDNA solution was used for amplification according to the amplification kit; all experiments were performed for 40 amplification cycles on the Biological System 7500 system according to the manufacturer's instructions. The primers used in this study are shown in Table 1, the threshold cycle (Ct) of the target product was normalized to the internal reference β-actin, and the relative expression was calculated using the comparative cycle threshold (ΔΔCt) method. 2.5.6 Enzyme-linked immunosorbent assay.The blood samples were collected from the abdominal aorta of rats and placed at room temperature for 1h. After the serum was centrifuged at 3000g at 4℃ for 20min, the supernatant was collected and the contents of IL-1β and IL-18 in serum were detected by enzyme-linked immunosorbent assay kit. In a few words, 100μl capture antibody was coated at 4 ° C, washed three times, and 200μl assay diluent was blocked at room temperature for 1h. Then 100μl standard dilutions of IL-1β and IL-18 were added and incubated at 37 ° C for 1h. After repeated washing, substrate was added to each well and incubated at room temperature for 20min. The quantitative absorbance was then obtained by enzyme-linked immunosorbent assay at 450nm according to IL-1β and IL-18 protein standards. 2.6 Statistical analysis - SPSS20.0 ( IBM U S) statistical software was used to examine all of the data. The experiment results were expressed as mean ± standard deviation ( ±s ). For group comparisons, a one-way ANOVA was performed. Statistical significance was defined as P ≤0.05. 3. Results 3.1 Electroacupuncture has neuroprotective effects on neurological function in MCAO rats Compared with the model group, the neurological function score and cerebral infarction volume in the EA group and the inhibitor group had no significant changes after 1 day of intervention (p > 0.05). On the 7 and 14 days of intervention, compared with the model group, the neurological function injury score and cerebral infarction volume in the EA group and the inhibitor group were reduced (p < 0.05, FIG. 1 and 2). At the same time, Nissl staining showed that the morphology and number of neuronal cells in the 14th day group. Compared with the model group, the number of Nissl bodies in the EA group and the inhibitor group was significantly increased (p < 0.01), and the cell morphology was more complete (FIG. 3). These results suggest that EA can improve neurological function scores and reduce cerebral infarction volume, which is similar to the neuroprotective effect of the inhibitor group. 3.2 The expression of NLRP3/GSDMD in the brain of rats with cerebral ischemia-reperfusion after electroacupuncture intervention NLRP3 and GSDMD were mainly expressed in the cytoplasm and co-stained with DAPI. Double immunostaining showed that NLRP3 and GSDMD co-existed (Figure 4). Compared with the model group, the number of positive cells in the EA group and the inhibitor group was significantly reduced (p < 0.05, p < 0.01). 3.3 Gene expression levels of GSDMD and NLRP3 in brain tissue Compared with the sham-operation group, the expression levels of GSDMD and NLRP3 mRNA in the model group were significantly increased (p<0.05). Compared with the model group, the EA group and the inhibition group had significant reductions in the mRNA expression levels of GSDMD and NLRP3 (p<0.05). See Figure 5. 3.4 The expression levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay The expression levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. Compared with the sham operation group, the expression levels of IL-1β and IL-18 were increased after 1, 7, and 14 days of treatment (p > 0.05). Compared with the model group, the expressions of IL-1β and IL-18 in the EA group and the inhibitor group were significantly decreased (p < 0.01). See Figs. 6 and 7. 3.5 The protein expression levels of GSDMD, NLRP3, Caspase-1, IL-1β and IL-18 in brain tissue were detected Compared with the sham-operation group, the expression levels of GSDMD, Caspase-1, IL-1β and NLRP3 protein in the model group were significantly increased (p<0.05). Compared with the model group, the expression levels of NLRP3, GSDMD, Caspase-1, IL-1β and IL-18 proteins in the EA group were significantly decreased at different time points (p<0.05). See Figures 8, 9, and 10. 4. Discussion EA is a preventative and therapeutic approach for stroke that combines traditional acupuncture and electrotherapy. It has a sizable impact on lowering the severity, neurological function, and aftereffects of ischemic stroke, also it is safe to use and administer. In clinical practice, EA treatment is commonly administered to stroke patients through the acupoints of DaiZhui (DU14) and BaiHui (DU20)[ 8 ]. EA stimulation at the acupoints DU14 and DU20 has been proven in a number of studies to have neuroprotective benefits in rats suffering from cerebral ischemia[ 9 ]. In this study, DU14 and DU20 acupoints were selected to evaluate the effect of EA treatment on MCAO rat model to study its potential mechanism. The neurological function score is an essential indicator for evaluating brain function impairment, which can visually and accurately reflect the degree of brain damage after cerebral ischemia and recovery after treatment. Previous studies have demonstrated the positive effects of electroacupuncture stimulation on reducing post-ischaemic brain injury and promoting neurological recovery[ 10 ] Our study showed a statistically significant improvement in neurological function scores after electro-acupuncture treatment compared to the MCAO group. Nissl body as an important indicator of response to nerve function, decrease or even disappear when nerve function is impaired. Our study has shown that the number of Nissl body was significantly increased in the electroacupuncture group compared to the MCAO group, indicating that electroacupuncture can promote nerve function recovery. TTC staining of brain sections also showed the same results, with smaller infarct volumes in the electroacupuncture group than in the MCAO group. These results suggest that electroacupuncture can promote nerve function repair after ischemic stroke. Extensive data suggests that neuroinflammation plays an important role in brain injury following ischemia-reperfusion trauma[ 11 – 12 ]. We speculate that electroacupuncture may inhibit neuroinflammation and promote nerve function repair in ischemic stroke. Studies have shown that microglia are activated after cerebral ischemia, producing large amounts of neurotoxic molecules and pro-inflammatory cytokines that exacerbate brain damage[ 13 – 17 ]. Because of their prevalence in the central nervous system, NLRP3 inflammatory vesicles are highly concerned [ 18 – 20 ]. In ischemic brain injury, the NLRP3 inflammasome is crucial in mediating inflammation[ 21 ]. The essential components are NLRP3, ASC, and caspase-1[ 22 ]. The entire assembly of the NLRP3 inflammasome is activated when it is stimulated by endogenous or external activating irritants[ 23 – 25 ]. Activated NLRP3 activates caspase-1, which enhances IL-1 and IL-18 biosynthesis[ 26 ] and drives inflammatory responses through various downstream signaling pathways, resulting in neuronal damage[ 27 ]. Our Western blotting results, which demonstrated increased expression of NLRP3 and caspase-1 in the MCAO group, supported this. Notably, the expression of NLRP3 and caspase-1 decreased in the EA group, and the difference was statistically significant compared with that in the MCAO group. We hypothesize that electroacupuncture inhibits the activation of NLRP3 inflammatory vesicles and attenuates the release of the inflammatory mediators IL-1β and IL-18. Over-activation of NLRP3 inflammatory vesicles can trigger a cascade of inflammatory responses, culminating in a new form of cell death — pyroptosis[ 28 ]. As our results indicate that significantly higher NLRP3 expression was shown with more severe nerve damage in the MCAO group compared to the sham group. We use diaminobenzidine (DAB) to detect intracellular peroxidase activity in TUNEL fluorescent staining, with obvious brownish-yellow cells in the MCAO group. In contrast, the cells in the sham and electroacupuncture groups were not necrotic and did not react with the marker, with a significant number of normal blue cells being visible. The increase in normal cells in the electroacupuncture treatment group suggests that electroacupuncture treatment can reduce neuroinflammation and promote neuronal cells. EA has been shown in studies to alleviate neuroinflammation by reducing the expression of NLRP3/Caspase-1 inflammasome. In conclusion, elevated levels of NLRP3 in MCAO rats are an important cause of brain injury, inhibition of NLRP3 activation or reduction of its level may be a potential target for the treatment of cerebral ischemic injury. As forementioned, EA therapy at the DU14 and DU20 acupoints improved neurological function and reduced cerebral infarction. Furthermore, EA significantly reduced NLRP3 and caspase-1 levels in the peri-infarct cortex, resulting in reduced ischemia/reperfusion-induced inflammatory damage in the brain. The current findings indicate that EA protects the brain from ischemia/reperfusion injury, at least in part via NLRP3/caspase-1 regulation. EA therapy enhances neurological functional recovery and reduces inflammatory responses. Its underlying mechanism maybe related to the regulating of NLRP3/caspase-1. According to this study's findings, EA may have a distinct mechanism of action for treating ischemic brain injury. Declarations Acknowledgments This work was supported by the National Research Foundation of China Grant funded by the China Government (81860881,81860869). General project of Yunnan applied basic research program( 202201AT070214,202001AZ070001-020).Two types of talent projects in Yunnan Province(202205AD160024). Data Availability The experimental data supporting this study’s findings are available from the corresponding authors upon reasonable request. Conflicts of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical Approval The experimental animal center at Kunming Medical University is where all of the animals were raised, and their qualification certificate number was SCXK (Dian) K2020-0015. The animals in this experiment were disposed of according to the 2006 Guideline of the Chinese Ministry of Science and Technology for the Care and Use of Laboratory Animals. Author Contribution All authors listed have made a substantial contribution to the work, and approved it for publication. References Shuang X (2020) Zhu Yicheng.Gender differences in stroke:epidemiology, risk factors,treatment, and prognosis[J]. 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Cell Microbiol 10:238 [J] Karmakar M et al N-GSDMD trafficking to neutrophil organelles facilitates IL-1beta release independently of plasma membrane pores and pyroptosis[J].Immunol.2020,11(12):2212–2225 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3791862","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":263360961,"identity":"01eb4ad0-0d40-4954-a11f-a1b3a725c095","order_by":0,"name":"Jian Wang","email":"","orcid":"","institution":"The First Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Wang","suffix":""},{"id":263360962,"identity":"5e08f0eb-d2b3-4575-b03b-b50aa77dbadb","order_by":1,"name":"Yujiang Xi","email":"","orcid":"","institution":"The First Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":false,"prefix":"","firstName":"Yujiang","middleName":"","lastName":"Xi","suffix":""},{"id":263360963,"identity":"09127fe8-3ebf-40eb-8ead-36f74a0d7a92","order_by":2,"name":"ZhiFeng Wang","email":"","orcid":"","institution":"The First Clinical Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":false,"prefix":"","firstName":"ZhiFeng","middleName":"","lastName":"Wang","suffix":""},{"id":263360964,"identity":"609cd85c-3800-4e57-a199-cbf6e203623b","order_by":3,"name":"LiWei Xing","email":"","orcid":"","institution":"College of Acupuncture and Massage, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":false,"prefix":"","firstName":"LiWei","middleName":"","lastName":"Xing","suffix":""},{"id":263360965,"identity":"c0b514bb-f912-4160-afe8-1c7cec0d8b1e","order_by":4,"name":"kun Zhang","email":"","orcid":"","institution":"College of Acupuncture and Massage, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":false,"prefix":"","firstName":"kun","middleName":"","lastName":"Zhang","suffix":""},{"id":263360966,"identity":"3b9afa47-8d79-4dc9-a82e-06b76a01f655","order_by":5,"name":"Xiaoyu Zhang","email":"","orcid":"","institution":"College of Acupuncture and Massage, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Zhang","suffix":""},{"id":263360967,"identity":"09c36839-165d-4c46-be60-82f95a1b8f9c","order_by":6,"name":"Pan Pan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYBACPgYGNiDFzAPEBw58+EGEFjaEFrbEgzN7SNACxDzGhznYiNHCfvjYgx8V1jL87T0fDjPwMMjzix0goIUnLd2w50w6j8SZsxsOF1gwGM6cnUDIYTlmErxth3kYbuRuODyDhyHB4DYhLfxvzCT/ArXI38h5cJiHjRgtEjlm0iBbDG7kMBCr5VmatAzQL4ZnjhkAA1mCsF/4+ZOPSb6psLaXO978+MOHHzby/NIEtKADCdKUj4JRMApGwSjADgBTJz+3wUNC9AAAAABJRU5ErkJggg==","orcid":"","institution":"College of Acupuncture and Massage, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, China","correspondingAuthor":true,"prefix":"","firstName":"Pan","middleName":"","lastName":"Pan","suffix":""}],"badges":[],"createdAt":"2023-12-22 12:14:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3791862/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3791862/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49077707,"identity":"a9e84730-9f4f-4748-9498-485d5dcc3011","added_by":"auto","created_at":"2024-01-02 19:09:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":465780,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of neurological deficit scores in each group (x±s,8 rats/group)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eNote: Compared with the model group, * p \u0026lt; 0.05, ** p \u0026lt; 0.01, **** p \u0026lt; 0.001, cranial nerve function was scored according to the neurological function evaluation table.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/4a23c78d9b387eac5154283a.png"},{"id":49077712,"identity":"68d49dba-716e-4ef5-9ed3-846c43d0cce5","added_by":"auto","created_at":"2024-01-02 19:09:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":873438,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVolume of cerebral infarction after EA treatment (x±s,8 rats/group)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: Panel A, B and C show the volume of cerebral infarction on day 1, 7 and 14, and panel D shows the volume change of cerebral infarction in rats. Compared with the model group, *** p \u0026lt; 0.001, **** p \u0026lt; 0.0001.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/ccf51db2e2e516e846e29145.png"},{"id":49078506,"identity":"fb55c8d7-62e0-4180-b528-2c72b3b911d0","added_by":"auto","created_at":"2024-01-02 19:17:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":857071,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNumber of Nissl bodies in Rats at Day 14 (x±s,8 rats/group).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: After 14 days of EA intervention, compared with the model group, **p \u0026lt; 0.01 (scale = 400μm), the number of Nissl bodies in the striatum of Nissl staining was observed.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/fc3be8ce1bfc35db17740d46.png"},{"id":49077711,"identity":"6bac49c0-b5d5-4be8-b7dc-14cd35707c66","added_by":"auto","created_at":"2024-01-02 19:09:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1716637,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNLRP3/GSDMD expression in the brain of rats with ischemia-reperfusion (x±s,8 rats/group)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: Immunofluorescence staining showed the expression and localization of NLRP3 and GSDMD in each group. NLRP3 and GSDMD were mainly expressed in the cytoplasm and co-stained with DAPI. Double immunostaining showed that NLRP3 and GSDMD co-existed. Compared with the model group, *p\u0026lt;0.05, **p \u0026lt; 0.01 (scale = 400μm).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/aea50fc636da26009aedfb09.png"},{"id":49077717,"identity":"1b527325-ad63-414b-a7c8-7ab9bd45c230","added_by":"auto","created_at":"2024-01-02 19:09:52","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":313750,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression Levels of NLRP3 and GSDMD genes in Rats at the 14th day (x±s,8 rats/group).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: realtime fluorescence quantitative PCR (q-PCR) was used to detect the expression levels of NLRP3 and GSDMD genes in the brain tissue of rats with ischemia-reperfusion after 14 days of intervention. The expression levels of NLRP3 and GSDMD in the EA group and the inhibitor group were significantly decreased, and the differences were statistically significant (*p \u0026lt; 0.05, **p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/b5d48299d5bebec8a4411154.png"},{"id":49077714,"identity":"f3f3aee6-70d7-4c15-b850-106eae30fd36","added_by":"auto","created_at":"2024-01-02 19:09:52","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":603028,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIL-1β Expression in Each Group (x±s,8 rats/group).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNotes: Panels A, B, and C show IL-1β expression levels on days 1, 7, and 14, and panel D shows changes in IL-1β expression levels on each day. Compared with the model group, the expression of IL-1β in the EA group and the inhibitor group was significantly decreased (**p \u0026lt; 0.01, ***p \u0026lt; 0.001, ****p \u0026lt; 0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/47caf676ef0ac32b0b96860a.png"},{"id":49077708,"identity":"c4f4fa73-3e46-4f92-9a48-c0a679b95ef6","added_by":"auto","created_at":"2024-01-02 19:09:51","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":540871,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIL-18 Expression in Each Group (x±s,8 rats/group).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: Panels A, B, and C show IL-18 expression levels on days 1, 7, and 14, and panel D shows the changes in IL-18 expression levels on each day. Compared with the model group, the expression of IL-18 in the EA group and the inhibitor group was significantly decreased (**p \u0026lt; 0.01, ***p \u0026lt; 0.001, ****p \u0026lt; 0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/0e3b38da431e42552424df11.png"},{"id":49078507,"identity":"3f0b6f84-0fb2-4787-ab50-8bc460aa29a8","added_by":"auto","created_at":"2024-01-02 19:17:51","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":318124,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression of NLRP3/ Caspase-1 inflammatory pathway-related proteins on day 1 (x±s,8 mice/group)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: Compared with the model group, the expressions of NLRP3, GSDMD, caspase-1, IL-1β and IL-18 proteins in the EA group and the inhibitor group were different on the first day of treatment (* p \u0026lt; 0.05, ** p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/e846fe6638d1080c1e74bbbf.png"},{"id":49078508,"identity":"eb47e956-a526-4890-b91d-b6db80b9fb57","added_by":"auto","created_at":"2024-01-02 19:17:52","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":295444,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression of NLRP3/ Caspase-1 inflammatory pathway-related proteins on day 7 (x±s,8 mice/group)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: On day 7, compared with the model group, the protein expressions of NLRP3, GSDMD, caspase-1, IL-1β and IL-18 in the EA group and the inhibitor group were significantly different (* p \u0026lt; 0.05, ** p \u0026lt; 0.01, *** p \u0026lt; 0.0001, **** p \u0026lt; 0.00001).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/0c04bd438c9f6bb40a2d3de7.png"},{"id":49078738,"identity":"76b1fbf1-312d-46c2-adee-7e78591e3385","added_by":"auto","created_at":"2024-01-02 19:25:51","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":301747,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExpression of NLRP3/ Caspase-1 inflammatory pathway-related proteins on day 14 (x±s,8 mice/group).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote: On day 14 after treatment, compared with the model group, the expression levels of NLRP3, GSDMD, caspase-1, IL-1β and IL-18 proteins in the EA group were significantly different (** p \u0026lt; 0.01, *** p \u0026lt; 0.0001, **** p \u0026lt; 0.00001).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/dacea52768eb496e146170a4.png"},{"id":49078953,"identity":"9f259137-3036-4798-9401-6ab45a0d9daa","added_by":"auto","created_at":"2024-01-02 19:41:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4813341,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3791862/v1/adf82491-520e-4274-8432-5b96be9f29d6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of Electroacupuncture on Neural Function and Expression of Inflammation-Related Proteins NLRP3/Caspase-1 in Rats with Ischemic Stroke","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eIschemic stroke is a potentially fatal cerebrovascular condition defined by a sudden decrease in blood supply to specific brain parts. It is the leading cause of permanent disability and the second largest cause of mortality worldwide. Around 14\u0026nbsp;million people suffer from strokes each year globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Inflammatory response, autophagy, oxidative stress, and apoptosis are now widely acknowledged as being critical pathogenic pathways in the development of ischemic stroke[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Numerous ischemic cascade events follow an ischemic stroke, with neuroinflammatory damage playing a significant role in the injury process. Anti-inflammatory therapy might treat ischemic stroke as a novel therapeutic option. Numerous studies have demonstrated that activation of multiprotein complexes\u0026mdash;inflammasomal NLRP3 plays a crucial role in metabolic disorders and various diseases including gout, heart disease, autoimmune diseases, and stroke[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, anticoagulation, antiplatelet aggregation, thrombolysis, neuroprotective medicines, and vasodilator medications are utilized to treat ischemic stroke. These medications have some efficacy but are time-dependent and have certain negative effects[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Electroacupuncture therapy is gaining popularity as more and more clinical trials show it to be safe and efficient in treating ischemic cerebral infarction[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Following an ischemic stroke, a series of events known as the \"ischemia cascade\" raise the levels of pro-inflammatory mediators including IL-18 and IL-1, which damage healthy neurons and exacerbate the initial ischemic damage. Noticeably, NLRP3 can play a crucial role in coordinating host physiology and shaping central and peripheral immune/inflammatory responses through the release of IL-18, and IL-1β. Additionally, numerous investigations have demonstrated that NLRP3 activation is essential for ischemic stroke injury[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. On the basis of previous research, this study investigated the possible mechanism of electroacupuncture in reducing nerve injury in ischemic stroke utilizing NLRP3/caspase-1 inflammatory pathway.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003e2.1 Animals\u003c/p\u003e\n\u003cp\u003eForty-eight SPF male SD rats, weighing 220\u0026plusmn;10g, were provided by the Experimental Animal Center at Kunming Medical University. The experimental animal center at Kunming Medical University is where all of the animals were raised, and their qualification certificate number was SCXK (Dian) K2020-0015. The feeding temperature was set at 23 2\u0026deg;C with a 60% humidity level and a 12-hour light-dark cycle. The usual feed was given, with free access to food and drink. Each group of 12 rats was randomly divided into four groups: sham operation group, model operation group, electroacupuncture group and inhibitor group. The animals in this experiment were disposed of according to the 2006 Guideline of the Chinese Ministry of Science and Technology for the Care and Use of Laboratory Animals.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.2 Reagents and instruments\u003c/p\u003e\n\u003cp\u003eThe reagents and instruments used in this research included\u0026nbsp;a digital medical image analysis system (MOTIC Asia Optical Technology Co,Ltd), an electroacupuncture equipment (HANS-200A, Jisheng Medical instrument Co, Ltd,Nanjing,China), \u0026nbsp;stainless disposable acupuncture needles (Hwato,0.18mm\u0026times;13mm, Suzhou Medical Equipment Factory, Suzhou, China), Alexa Fluor\u003csup\u003e\u0026reg;\u003c/sup\u003e488Donkey Anti-Rabbit IgG Antibody (Invitrogen Reagent Corporation, Carlsbad,United States), Bicinchoninic acid protein quantification test kit (Beyotime Institute of Biotechnology,Jiangsu, China),\u0026nbsp;primary antibody\u0026nbsp;diluent for WB (GTX28208) (Beyotime Institute of Biotechnology, Jiangsu, China), Anti-Bax Monoclonal,Anti-BCL2 Polyclonal Antibody, \u0026nbsp;Anti-Cleaved-caspase-3 (Asp175) antibody ( Biotechnology Santa Cruz Co, Ltd, Texas, United States), ammonium persulfate (MYM Biological Technology Company Limited, Chicago, IL, USA), polyvinylidene fluoride membrane (Invitrogen Reagent Corporation, Carlsbad, United States),In Situ Cell Apoptosis TUNEL Detection kit, (Hoffmann-La Roche Co, Ltd), and Reagent for glycine,56-40-6(Biosharp Biotechnology life science Co, Ltd, Anhui, China), 30% acrylamide and BIO-BEST 300M gel imaging analysis system \u0026nbsp;(Solarbia Science and Biotechnology Co, Ltd, Beijing, China), Ultra High Sensitivity ECL chemiluminescence kit, batch number:50018 (Beyotime Institute of Biotechnology, Jiangsu, China).\u003c/p\u003e\n\u003cp\u003e2.3 Ischemic stroke model\u003c/p\u003e\n\u003cp\u003eFor the model group and electroacupuncture group, an ischemic stroke model was created and detailed elsewhere. The following were the detailed procedures: after anesthesia, 3.5 percent pentobarbital sodium was administered intraperitoneally, and a neck incision was operated with tissue separated layer by layer. The external carotid artery (ECA), the internal carotid artery (ICA), and the left common carotid artery (CCA) were all exposed and then separated. The ECA is bundled and separated, as w well as its branches. After making a small cut at the beginning of the ECA residual, a smooth suture embolization was placed into the intracranial section of the intracranial segment of the ICA. The suture embolus was inserted at a depth of approximately 18 \u0026plusmn; 0.5 cm from the carotid bifurcation. The blood supply to the internal carotid artery and middle cerebral artery can be restored by returning the bulb of the external carotid artery to the external carotid artery during perfusion and by embolization via the external suture. After ensuring correct postoperative surgery and observing for abnormalities, the skin was sutured and the animals were placed back in their cages. Insulation feeding was given, as well as observation. Animals were examined for ischemia within the time limit to exclude animals with intact limbs or those that had died. In the sham-operated group, only the left common carotid artery was isolated and no other treatment was performed. The suture embolization was removed one and a half hours after surgery, and no thrombus or bleeding was seen in the ICA, indicating successful reperfusion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.4 Intervention methods\u003c/p\u003e\n\u003cp\u003eThe electroacupuncture group:\u0026nbsp;after modeling, an electroacupuncture intervention was performed on day 1. Acupoint selection was done according to Hua Xingbang et al \u0026quot;Development of Rat Acupoint Sites.\u0026quot;. BaiHui (DU20)\u0026quot; (middle of parietal bone of rats) and \u0026quot;DaiZhui (DU14)\u0026quot; (in the depression of the seventh cervical spine\u0026apos;s subspinal process in the prone position on the posterior median line)[13]. Among them, acupuncture was performed at \u0026quot;Baihui\u0026quot; point about 2mm in a percutaneous oblique direction to the forehead along the median line of the brain, and at \u0026quot;Dazhui\u0026quot; point directly for 5mm. After the needling, Hans-200 electroacupuncture instrument was used to select density wave with a frequency of 2Hz/100Hz and an intensity of 1mA. The needles were left in place for 30 minutes, and then electro-acupuncture was utilized once a day for two weeks, after which the procedure was repeated. To avoid upsetting the rats, the entire treatment was carried out quickly, gently, and smoothly. No interventions were given to either the model control group or the sham operation group.\u003c/p\u003e\n\u003cp\u003e2.5 Methods of indicator detection\u003c/p\u003e\n\u003cp\u003e2.5.1 Neurological deficit score.Zea Longa\u0026apos;s 5-point scoring method was used to evaluate the degree of neurological deficit in rats. The neurological deficit score was 0, with no obvious defect; 1 point, the right forepaw was not fully extended; 2 points, turning to the opposite side; 3 points, fall to the opposite side; 4 points, no spontaneous walking or loss of consciousness.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.5.2 TTC staining. After the neurological deficit score was completed, 6 rats in each group were randomly selected and sacrificed under anesthesia for brain tissue harvesting. TTC staining was used to stain the meningeal sections, and the stained brain slices of rats in each group were photographed using a digital camera. Image Pro-Plus(Version 6.0) software was used to investigate and calculate the infarct size, and the infarct size was calculated by the investigator. The formula was as follows: percentage of infarction (percentage)=[pale area mass /(pale area mass + non-pale area mass)]\u0026times;100%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.5.3 Nissl staining. After conventional dewaxing and hydration, paraffin sections were immersed in tar purple staining solution, baked at 56\u0026deg;C for 1h, and immersed in 0.5% hydrochloric acid ethanol fractionation solution for 4-20s. After dehydration, the sections were sealed with neutral gel and stored away from light. A 400-fold light microscope was used to investigate the morphological and structural alterations in the rat brain.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.5.4 Western blot. With 200 microliter of RIPA lysate (containing protease inhibitor), 80 mg of damaged brain tissue was homogenized. The entire protein in each rat\u0026apos;s brain tissue was extracted. BCA was used to calculate the sample protein concentration, and denaturation was done in a metal bath at 95\u0026deg;C for 10 minutes. Sample loading, electrophoresis, membrane transfer, blocking with 5% skim milk powder for 2 hours, overnight at 4 \u0026deg;C, primary antibody incubation against caspase-1, NLRP3, and microtubulin (1SDS-PAGE 3000), membrane washing, and secondary antibody incubation (sheep anti-mouse IgG 1:10 00 and sheep anti-rabbit IgG 1:10 00). ecl hypersensitive Chemiluminescent solutions were uniformly distributed and photographed using an ECL imaging system. Image Pro Plus software was used to assess the gray value of each target protein/\u0026beta;-tubulin, and the gray value of the strips was used to detect the relative expression intensity of the target protein.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.5.5 Real-time fluorescent quantitative PCR.RNA was extracted from the brain tissue of each group, and cDNA was synthesized according to the reverse transcription kit. The cDNA was used as a template for PCR reaction on a fluorescence quantitative PCR instrument. Primers were synthesized by Guangzhou Ruibo Biological Co., LTD. See Table 1 for details. Total RNA was extracted with Trizol reagent, 1\u0026mu;g of total RNA was reverse transcribed with a reverse transcription kit, and 2\u0026mu;l of first-strand cDNA solution was used for amplification according to the amplification kit; all experiments were performed for 40 amplification cycles on the Biological System 7500 system according to the manufacturer\u0026apos;s instructions. The primers used in this study are shown in Table 1, the threshold cycle (Ct) of the target product was normalized to the internal reference \u0026beta;-actin, and the relative expression was calculated using the comparative cycle threshold (\u0026Delta;\u0026Delta;Ct) method.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg 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\" width=\"537\" height=\"666\"\u003e\u003c/p\u003e\n\u003cp\u003e2.5.6 Enzyme-linked immunosorbent assay.The blood samples were collected from the abdominal aorta of rats and placed at room temperature for 1h. After the serum was centrifuged at 3000g at 4℃ for 20min, the supernatant was collected and the contents of IL-1\u0026beta; and IL-18 in serum were detected by enzyme-linked immunosorbent assay kit. In a few words, 100\u0026mu;l capture antibody was coated at 4 \u0026deg; C, washed three times, and 200\u0026mu;l assay diluent was blocked at room temperature for 1h. Then 100\u0026mu;l standard dilutions of IL-1\u0026beta; and IL-18 were added and incubated at 37 \u0026deg; C for 1h. After repeated washing, substrate was added to each well and incubated at room temperature for 20min. The quantitative absorbance was then obtained by enzyme-linked immunosorbent assay at 450nm according to IL-1\u0026beta; and IL-18 protein standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.6 Statistical analysis\u003c/p\u003e\n\u003cp\u003e- \u0026nbsp;SPSS20.0 (\u003cem\u003eIBM U\u003c/em\u003eS) statistical software was used to examine all of the data. The experiment results were expressed as mean \u0026plusmn; standard deviation (\u003cstrong\u003e\u0026plusmn;s\u003c/strong\u003e). For group comparisons, a one-way ANOVA was performed. Statistical significance was defined as \u003cem\u003eP\u003c/em\u003e\u0026le;0.05.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1\u0026nbsp;\u003c/strong\u003eElectroacupuncture has neuroprotective effects on neurological function in MCAO rats\u003c/p\u003e\n\u003cp\u003eCompared with the model group, the neurological function score and cerebral infarction volume in the EA group and the inhibitor group had no significant changes after 1 day of intervention (p \u0026gt; 0.05). On the 7 and 14 days of intervention, compared with the model group, the neurological function injury score and cerebral infarction volume in the EA group and the inhibitor group were reduced (p \u0026lt; 0.05, FIG. 1 and 2). At the same time, Nissl staining showed that the morphology and number of neuronal cells in the 14th day group. Compared with the model group, the number of Nissl bodies in the EA group and the inhibitor group was significantly increased (p \u0026lt; 0.01), and the cell morphology was more complete (FIG. 3). These results suggest that EA can improve neurological function scores and reduce cerebral infarction volume, which is similar to the neuroprotective effect of the inhibitor group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u0026nbsp;\u003c/strong\u003eThe expression of NLRP3/GSDMD in the brain of rats with cerebral ischemia-reperfusion after electroacupuncture intervention\u003c/p\u003e\n\u003cp\u003eNLRP3 and GSDMD were mainly expressed in the cytoplasm and co-stained with DAPI. Double immunostaining showed that NLRP3 and GSDMD co-existed (Figure 4). Compared with the model group, the number of positive cells in the EA group and the inhibitor group was significantly reduced (p \u0026lt; 0.05, p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3\u003c/strong\u003e Gene expression levels of GSDMD and NLRP3 in brain tissue\u003c/p\u003e\n\u003cp\u003eCompared with the sham-operation group, the expression levels of GSDMD and NLRP3 mRNA in the model group were significantly increased (p\u0026lt;0.05). Compared with the model group, the EA group and the inhibition group had significant reductions in the mRNA expression levels of GSDMD and NLRP3 (p\u0026lt;0.05). See Figure 5.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4\u0026nbsp;\u003c/strong\u003eThe expression levels of IL-1\u0026beta;\u0026nbsp;and IL-18 were detected by enzyme-linked immunosorbent assay\u003c/p\u003e\n\u003cp\u003eThe expression levels of IL-1\u0026beta;\u0026nbsp;and IL-18 were detected by enzyme-linked immunosorbent assay. Compared with the sham operation group, the expression levels of IL-1\u0026beta;\u0026nbsp;and IL-18 were increased after 1, 7, and 14 days of treatment (p \u0026gt; 0.05). Compared with the model group, the expressions of IL-1\u0026beta;\u0026nbsp;and IL-18 in the EA group and the inhibitor group were significantly decreased (p \u0026lt; 0.01). See Figs. 6 and 7.\u003c/p\u003e\n\u003cp\u003e3.5 The protein expression levels of GSDMD, NLRP3, Caspase-1, IL-1\u0026beta; and IL-18 in brain tissue were detected\u003c/p\u003e\n\u003cp\u003eCompared with the sham-operation group, the expression levels of GSDMD, Caspase-1, IL-1\u0026beta; and NLRP3 protein in the model group were significantly increased (p\u0026lt;0.05). Compared with the model group, the expression levels of NLRP3, GSDMD, Caspase-1, IL-1\u0026beta; and IL-18 proteins in the EA group were significantly decreased at different time points (p\u0026lt;0.05). See Figures 8, 9, and 10.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eEA is a preventative and therapeutic approach for stroke that combines traditional acupuncture and electrotherapy. It has a sizable impact on lowering the severity, neurological function, and aftereffects of ischemic stroke, also it is safe to use and administer. In clinical practice, EA treatment is commonly administered to stroke patients through the acupoints of DaiZhui (DU14) and BaiHui (DU20)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. EA stimulation at the acupoints DU14 and DU20 has been proven in a number of studies to have neuroprotective benefits in rats suffering from cerebral ischemia[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this study, DU14 and DU20 acupoints were selected to evaluate the effect of EA treatment on MCAO rat model to study its potential mechanism.\u003c/p\u003e \u003cp\u003eThe neurological function score is an essential indicator for evaluating brain function impairment, which can visually and accurately reflect the degree of brain damage after cerebral ischemia and recovery after treatment. Previous studies have demonstrated the positive effects of electroacupuncture stimulation on reducing post-ischaemic brain injury and promoting neurological recovery[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Our study showed a statistically significant improvement in neurological function scores after electro-acupuncture treatment compared to the MCAO group. Nissl body as an important indicator of response to nerve function, decrease or even disappear when nerve function is impaired. Our study has shown that the number of Nissl body was significantly increased in the electroacupuncture group compared to the MCAO group, indicating that electroacupuncture can promote nerve function recovery. TTC staining of brain sections also showed the same results, with smaller infarct volumes in the electroacupuncture group than in the MCAO group. These results suggest that electroacupuncture can promote nerve function repair after ischemic stroke.\u003c/p\u003e \u003cp\u003eExtensive data suggests that neuroinflammation plays an important role in brain injury following ischemia-reperfusion trauma[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. We speculate that electroacupuncture may inhibit neuroinflammation and promote nerve function repair in ischemic stroke. Studies have shown that microglia are activated after cerebral ischemia, producing large amounts of neurotoxic molecules and pro-inflammatory cytokines that exacerbate brain damage[\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Because of their prevalence in the central nervous system, NLRP3 inflammatory vesicles are highly concerned [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In ischemic brain injury, the NLRP3 inflammasome is crucial in mediating inflammation[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The essential components are NLRP3, ASC, and caspase-1[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The entire assembly of the NLRP3 inflammasome is activated when it is stimulated by endogenous or external activating irritants[\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Activated NLRP3 activates caspase-1, which enhances IL-1 and IL-18 biosynthesis[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and drives inflammatory responses through various downstream signaling pathways, resulting in neuronal damage[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Our Western blotting results, which demonstrated increased expression of NLRP3 and caspase-1 in the MCAO group, supported this. Notably, the expression of NLRP3 and caspase-1 decreased in the EA group, and the difference was statistically significant compared with that in the MCAO group. We hypothesize that electroacupuncture inhibits the activation of NLRP3 inflammatory vesicles and attenuates the release of the inflammatory mediators IL-1β and IL-18. Over-activation of NLRP3 inflammatory vesicles can trigger a cascade of inflammatory responses, culminating in a new form of cell death \u0026mdash; pyroptosis[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. As our results indicate that significantly higher NLRP3 expression was shown with more severe nerve damage in the MCAO group compared to the sham group. We use diaminobenzidine (DAB) to detect intracellular peroxidase activity in TUNEL fluorescent staining, with obvious brownish-yellow cells in the MCAO group. In contrast, the cells in the sham and electroacupuncture groups were not necrotic and did not react with the marker, with a significant number of normal blue cells being visible. The increase in normal cells in the electroacupuncture treatment group suggests that electroacupuncture treatment can reduce neuroinflammation and promote neuronal cells. EA has been shown in studies to alleviate neuroinflammation by reducing the expression of NLRP3/Caspase-1 inflammasome. In conclusion, elevated levels of NLRP3 in MCAO rats are an important cause of brain injury, inhibition of NLRP3 activation or reduction of its level may be a potential target for the treatment of cerebral ischemic injury.\u003c/p\u003e \u003cp\u003eAs forementioned, EA therapy at the DU14 and DU20 acupoints improved neurological function and reduced cerebral infarction. Furthermore, EA significantly reduced NLRP3 and caspase-1 levels in the peri-infarct cortex, resulting in reduced ischemia/reperfusion-induced inflammatory damage in the brain. The current findings indicate that EA protects the brain from ischemia/reperfusion injury, at least in part via NLRP3/caspase-1 regulation. EA therapy enhances neurological functional recovery and reduces inflammatory responses. Its underlying mechanism maybe related to the regulating of NLRP3/caspase-1. According to this study's findings, EA may have a distinct mechanism of action for treating ischemic brain injury.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Research Foundation of China Grant funded by the China Government (81860881,81860869). General project of Yunnan applied basic research program( 202201AT070214,202001AZ070001-020).Two types of talent projects in Yunnan Province(202205AD160024).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experimental data supporting this study\u0026rsquo;s findings are available from the corresponding authors upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experimental animal center at Kunming Medical University is where all of the animals were raised, and their qualification certificate number was SCXK (Dian) K2020-0015. The animals in this experiment were disposed of according to the 2006 Guideline of the Chinese Ministry of Science and Technology for the Care and Use of Laboratory Animals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors listed have made a substantial contribution to the work, and approved it for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShuang X (2020) Zhu Yicheng.Gender differences in stroke:epidemiology, risk factors,treatment, and prognosis[J]. 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Cell Microbiol 10:238 [J]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarmakar M et al N-GSDMD trafficking to neutrophil organelles facilitates IL-1beta release independently of plasma membrane pores and pyroptosis[J].Immunol.2020,11(12):2212\u0026ndash;2225\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ischemic stroke, Neuroinflammation, Electroacupuncture, NLRP3, Caspase-1","lastPublishedDoi":"10.21203/rs.3.rs-3791862/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3791862/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e:To investigate the neuroprotective effects of electroacupuncture at Baihui and Dazhui on rats in an ischemia-reperfusion injury model.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Forty-eight SPF male SD rats were randomly divided into sham operation group, model group, EA group and inhibitor group, with 12 rats in each group, and the middle cerebral arteryOcclusion (MCAO) model was established using the wire embolization method, and the model was successfully replicated and treated by acupuncture at Baihui and Dazhui. The neurological function scores were evaluated by Zea Longa neurological deficit score on days 1, 7 and 14 after treatment, and the volume of cerebral infarction was measured by 2, 3, 5-triphenyltetrazolium chloride staining. Detection of nod-like receptor protein 3 (NLRP3) and GSDMD gene expression by real-time fluorescence quantitative PCR , Western blot detection of NLRP3, GSDMD, Caspase-1 and other protein expression levels in rat brain tissue , and microglia levels were observed by immunofluorescence staining; the expression levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked adsorption assay.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eCompared with the model group, the rats in the electroacupuncture group had significantly lower neurological deficit score (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05), significantly reduced brain infarct volume (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.05), significantly reduced NLRP3 and GSDMD gene expression (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05), reduced NLRP3, GSDMD, Caspase-1 and other protein expression water, IL-1β, IL-18 inflammatory factor expression were significantly reduced (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Electroacupuncture can improve the symptoms of neurological injury in rats with ischemic stroke model, and may play a neuroprotective role by inhibiting NLRP3/Caspase-1 inflammatory pathway and reducing the expression of cell scorch-related proteins.\u003c/p\u003e","manuscriptTitle":"Effects of Electroacupuncture on Neural Function and Expression of Inflammation-Related Proteins NLRP3/Caspase-1 in Rats with Ischemic Stroke","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 19:09:47","doi":"10.21203/rs.3.rs-3791862/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b73457f6-1dc7-458c-aa36-9f852a855a5c","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-02T19:09:49+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-02 19:09:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3791862","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3791862","identity":"rs-3791862","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}