Effect of Ligustrazine on Myocardial Ischemia/reperfusion Injury Through Upregulating UCP3

Abstract Background: The study aimed to investigate whether ligustrazine, a traditional Chinese medicine, could attenuate myocardial ischemia/reperfusion (I/R) injury and explore the potential mechanism.Methods: 32 Sprague-Dawley rats were divided equally into four groups: sham operation (S); (I/R); I/R + ligustrazine preconditioning (Lig); I/R + ligustrazine preconditioning + mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) (Lig + LND). Myocardial I/R model was established and ligustrazine was administered intraperitoneally 5 min prior to ischemia, LND was administered intraperitoneally 10 min prior to reperfusion. The infarct area (IA) was measured by Evans blue staining, where levels of Myocardial injury markers, malondialdehyde (MDA), superoxide dismutase (SOD), adenosine triphosphate (ATP) were detected. RT-PCR and Western Blot were adopted to measure the uncoupling protein 3 (UCP3) expression.Results: Compared to I/R group, the IA/area at risk (AAR) in Lig, and Lig + LND groups were significantly decreased, UCP3 levels of mRNA and protein were increased (P < 0.05). Compared to Lig group, the IA/AAR in Lig + LND group was significantly increased (P < 0.05). Ligustrazine pretreatment increased SOD, ATP activity, and decreased cardiac troponin I (cTnI), creatine kinase-muscle/brain (CK-MB), lactate dehydrogenase (LDH) and MDA activities. The effect of ligustrazine was reversed by LND.Conclusion: The present results indicated that ischemic preconditioning of ligustrazine might protect myocardium against I/R injury through upregulating UCP3 expression.