Comparison of different curative methods on endometriosis in rats

In: Chung-Hua Fu Ch'an K'o Tsa Chih · 2017 · vol. 13(6) , pp. 674–680 · doi:10.3877/cma.j.issn.1673-5250.2017.06.010 · W3032462321
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-07-17 ⓘ

This study found that recombinant human interferon-α-2b and leuprorelin reduced ectopic lesion volume in a rat endometriosis model, with both treatments significantly lowering VEGF and TNF-α protein expression compared to controls.

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This paper studied the therapeutic effects of recombinant human interferon-α-2b compared with leuprorelin in a rat model of abdominal wall endometriosis created by autologous uterine endometrium transplantation in 50 healthy female Sprague-Dawley rats. After random assignment, rats received interferon-α-2b (100,000 IU subcutaneously every 48 h for 3 doses), leuprorelin (20 μg/kg/day for 28 days), or saline for 28 days, and investigators assessed ectopic lesion volume after 4 weeks and measured VEGF and TNF-α in ectopic tissue. Both interferon-α-2b and leuprorelin significantly reduced ectopic lesion volume versus controls, and both were associated with lower VEGF and TNF-α expression, while interferon-α-2b’s lesion-volume effect was not statistically different from leuprorelin (P=0.076). The authors explicitly note that whether interferon-α-2b can replace leuprorelin in clinical use remains uncertain and requires larger-scale animal and evidence-based clinical data. This paper is centrally about endometriosis — it directly compares interferon-α-2b with leuprorelin efficacy in an experimental endometriosis (ectopic endometrium) rat model.

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Abstract

Objective To discuss therapeutic effects of recombinant human interferon-α-2b and leuprorelin on rat endometriosis (EMs) model. Methods From August to November, 2016, a total of 50 healthy specific pathogen fee(SPF) female Sprague-Dawley (SD) rats were chosen as research subjects. The rat model of abdominal wall EMs was established by autologous uterine transplantation. The successfully established rat EMs model were randomly divided into experimental group A (n=15), experimental group B (n=15) and control group (n=15)according to random number table. There were no significant differences among three groups in the aspects of basic information (P>0.05). The rats in experimental group A received 3 times of 100 000 U of recombinant human interferon-α-2b by subcutaneous injection every 48 h. The experimental group B was daily treated with leuprorelin 20 μg/kg by subcutaneous injection, a total of 28 days. The control group was daily given subcutaneous injection of saline 0.1 mL, a total of 28 days. After the end of 4 weeks treatment, the growth of ectopic lesions in 3 groups were observed, and the expression of vascular endothelial growth factor (VEGF) protein and tumor necrosis factor (TNF)-α protein in ectopic endometrium tissues were detected by immunohistochemical method. All experimental protocols were approved by the Institutional Animal Care and Use Committee. Results ① Among 50 EMs rats, the successful rate of EMs rat establishment model was 90% (45/50). ② After 4 weeks treatment, there was significant difference in ectopic lesions volume among three groups (F=139.332, P<0.001). Among them, the ectopic lesions volume of rats in experimental group A and experimental group B were both smaller than that of rats in control goup (LSD-t=13.460, 15.280; P<0.001); the ectopic lesions volume of rats in experimental group B was smaller than that of rats in experimental group A, which had no significant (LSD-t=1.820, P=0.076). Besides, there were significant differences in ectopic volume of rats before and after the treatment in experimental group A and B (t=9.413, 14.545; P<0.001). ③ After 4 weeks treatment, there were no significant in the expression of VEGF protein and TNF-α protein among 3 groups (F=224.261, 225.391; P<0.001). The expression of VEGF protein and TNF-α protein of experimental group A and B were significant lower than those of control group (experimental group A vs control group: LSD-t=17.258, 19.121; P<0.001; experimental group B vs control group: LSD-t=19.260, 17.552; P<0.001). Conclusions Recombinant human interferon-α-2b has therapeutic effect on rats with EMs. Downregulating the expression of VEGF and TNF-α is probably one of the mechanisms.Whether recombinant human interferon-α-2b can replace leuprolide as a new drug in clinical application or not, we still need large-scale animal experiments and evidence-based medicine to confirm. Key words: Endometriosis; Interferon alfa-2b; Leuprolide; Vascular endothelial growth factors; Tumor necrosis factor-alpha; Disease models, animal; Rats
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Objective

To discuss therapeutic effects of recombinant human interferon-α-2b and leuprorelin on rat endometriosis (EMs) model.

Methods

From August to November, 2016, a total of 50 healthy specific pathogen fee(SPF) female Sprague-Dawley (SD) rats were chosen as research subjects. The rat model of abdominal wall EMs was established by autologous uterine transplantation. The successfully established rat EMs model were randomly divided into experimental group A (n=15), experimental group B (n=15) and control group (n=15)according to random number table. There were no significant differences among three groups in the aspects of basic information (P>0.05). The rats in experimental group A received 3 times of 100 000 U of recombinant human interferon-α-2b by subcutaneous injection every 48 h. The experimental group B was daily treated with leuprorelin 20 μg/kg by subcutaneous injection, a total of 28 days. The control group was daily given subcutaneous injection of saline 0.1 mL, a total of 28 days. After the end of 4 weeks treatment, the growth of ectopic lesions in 3 groups were observed, and the expression of vascular endothelial growth factor (VEGF) protein and tumor necrosis factor (TNF)-α protein in ectopic endometrium tissues were detected by immunohistochemical method. All experimental protocols were approved by the Institutional Animal Care and Use Committee.

Results

① Among 50 EMs rats, the successful rate of EMs rat establishment model was 90% (45/50). ② After 4 weeks treatment, there was significant difference in ectopic lesions volume among three groups (F=139.332, P<0.001). Among them, the ectopic lesions volume of rats in experimental group A and experimental group B were both smaller than that of rats in control goup (LSD-t=13.460, 15.280; P<0.001); the ectopic lesions volume of rats in experimental group B was smaller than that of rats in experimental group A, which had no significant (LSD-t=1.820, P=0.076). Besides, there were significant differences in ectopic volume of rats before and after the treatment in experimental group A and B (t=9.413, 14.545; P<0.001). ③ After 4 weeks treatment, there were no significant in the expression of VEGF protein and TNF-α protein among 3 groups (F=224.261, 225.391; P<0.001). The expression of VEGF protein and TNF-α protein of experimental group A and B were significant lower than those of control group (experimental group A vs control group: LSD-t=17.258, 19.121; P<0.001; experimental group B vs control group: LSD-t=19.260, 17.552; P<0.001).

Conclusions

Recombinant human interferon-α-2b has therapeutic effect on rats with EMs. Downregulating the expression of VEGF and TNF-α is probably one of the mechanisms.Whether recombinant human interferon-α-2b can replace leuprolide as a new drug in clinical application or not, we still need large-scale animal experiments and evidence-based medicine to confirm. | [1] | Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis[J]. Fertil Steril, 2012, 98(3): 511-519. | | [2] | Kitawaki J, Kusuki I, Yamanaka K, et al. Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain[J]. Eur J Obstet Gynecol Reprod Biol, 2011, 157(2): 212-216. | | [3] | Surrey ES. Gonadotropin-releasing hormone agonist and add-back therapy: what do the data show?[J]. Curr Opin Obstet Gynecol, 2010, 22(4): 283-288. | | [4] | Altintas D, Kokcu A, Tosun M, et al. 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