Effect Of SIRT1 On The Expression Of Nrf2 In Resveratrol Alleviating Myocardial Ischemia-reperfusion Injury In Diabetic Rats

Objective: To investigate the effect of SIRT1 on the expression of Nrf2 in resveratrol alleviating myocardial ischemia-reperfusion injury in diabetic rats.Methods: forty adult male SD rats were used in this study.Type 2 diabetes mellitus was induced by high fat fed then intraperitoneal injection of STZ.All animals were randomly divided into 4 groups:sham operation group,ischemia reperfusion group(I/R group),resveratrol preconditioninggroup(R group),resveratrol preconditioning+ex527group(RE group).Rats in I/R group,R group,RE group were ligated with LDA for 30 min and followed by 120 min reperfusion to prepare models of myocardial ischemia reperfusion injury.R group and RE group were intraperitoneally injected with Res 15 mg/Kg for 7 days before the establishment of surgery,RE group was injected with SIRT1 inhibitor ex-527 1μg/kg at 15 minutes before ischemia myocardial.Blood samples were collected to measure the concentration of LDH and CK-MB by ELISA at the end of reperfusion.The rats were then killed in each group,and the heart was removed for measurement of myocardial infarct size by using TTC staining.Pathologic changes in myocardial tissues were observed by Hematoxylin and eosin(HE).The heart was removed for measuring content of MDA and activity of SOD.The expression of myocardial SIRT1,Nrf2,HO-1 protein were measured by Western blot.Results: Compared with the Sham group,myocardial infarct size,serum CK-MB,LDH levels increased,myocardial tissue MDA content increased,SOD activity decreased,SIRT1,Nrf2,and HO-1 protein expression decreased in the I/R group,R group,and RE group(P <0.05).Compared with the I/R group,the myocardial infarct size,serum CK-MB,LDH levels,myocardial tissue MDA content decreased,SOD activity increased,SIRT1,Nrf2 and HO-1 protein expression increased in the R and RE groups(P <0.05).Compared with the R group,myocardial infarct size,serum CK-MB,and LDH levels increased,myocardial tissue MDA content increased,SOD activity decreased,and SIRT1,Nrf2,and HO-1 protein expression decreased in the RE group(P<0.05).Conclusions:SIRT1 promotes the expression of Nrf2 in the myocardium of diabetic rats,and resveratrol reduces the myocardial ischemia reperfusion injury by activating the SIRT1/Nrf2 signaling pathway in diabetic rats.