Effect Of Mitophagy Activated By PINK1-parkin Pathway On Myocardial Protection Of Sevoflurane Postconditioning In Diabetic Rats

Objective:Observe the effect of mitophagy activated by PINK1-parkin pathway on the myocardial protective effect of sevoflurane postconditioning in diabetic rats,and find the reason of the disappearance of myocardial protective effect of sevoflurane postconditioning in diabetic rats on myocardial ischemia-reperfusion injury,in order to provide possible methods for treating the disease.Methods:Healthy adult male SD rats,weighing between 230-300 g,were prepared with a single intraperitoneal injection of 1% streptozotocin(STZ)50mg / kg to prepare diabetic rat models.According to the random number table method,50 rats with successful modeling were divided into 5 groups(n = 10),namely sham operation group(sham group),myocardial ischemia reperfusion group(IR group),myocardial ischemia reperfusion +sevoflurane postconditioning group(ISev group),myocardial ischemia-reperfusion +BAM15 group(IB group),myocardial ischemia-reperfusion + BAM15 + sevoflurane postconditioning group(IBSev group).In the IR group,ISev group,IB group,and IBSev group,the left anterior descending coronary artery(LAD)was ligated,and the suture was loosened after 30 minutes and reperfused for 120 minutes to construct a myocardial ischemia reperfusion(MIRI)model.The Sham group only threaded,not MIRI.The ISev group and the IBSev group started inhaling 2.5% sevoflurane 1 min before reperfusion for6 min.The IB group and the IBSev group were intraperitoneally injected with 1 mg / kg BAM15 1 hour before ischemia,and the other three groups were injected with the same volume of Dimethyl sulfoxide(DMSO)at the same time.Compare the HR,SBP and MAP of the rats in each group before ischemia(T0),before reperfusion(T1)and after reperfusion(T2);After 120 minutes of reperfusion,blood was taken to measure the serum c Tn I concentration,TTC staining method was used to measure the proportion of myocardial ischemia and infarction area in each group;and HE staining was used to observe the myocardial cell morphology;The expression of parkin protein was measured by Western blot.Results:The hemodynamic indexes of IR group,ISev group and IB group decreased sequentially at T0,T1 and T2,while IBSev group increased at T2,but still less than T0;There is no difference in the proportion of myocardial ischemic area between IR group,ISev group,IB group and IBSev group;Compared with the sham group,the HR,SBP,and MAP were reduced at T2 in each group,the myocardial cell structure was destroyed,the serum c Tn I concentration,the proportion of myocardial infarction area,and the expression of parkin protein were increased;Compared with the IR group,there is no significant difference in all indicators in the ISev group,and the myocardial injury indicators in the IB group and the IBSev group have improved.Compared with the IB group,the IBSev group had increased HR,SBP,and MAP,and the serum c Tn I and proportion of myocardial infarction area decreased.There was no significant difference in the expression of parkin protein.Conclusion:The protective effect of sevoflurane post-treatment on MIRI myocardium in diabetic rats disappeared,which may be related to the inhibition of mitophagy,and activation of the PINK1-parkin pathway may partially restore its protective effect.