Mechanism Of Sevoflurane Postconditioning-induced Myocardial Protection Invalidation In Diabetc Rats:the Relationship With Drp1 Activity

Objective:Interfering with the activity of dynamin related protein-1(Drp1),To investigate the irreversible damage of cardiomyocyte during myocardial ischemia-reperfusion injury in diabetic rats,and to determin the relationship between Drp1 activity and Mechanism of sevoflurane postconditioning-induced myocardial protection invalidation in diabetic rats.Methods:Healthy adult male Sprague-Dawley rats,weighing 225-275 g,Type 2 diabetes mellitus model was induced by high-fat and high-sucrose diet and intraperitoneal streptozotoein 30 mg/kg.Fasting blood glucose is measured once a week,for 4 consecutive weeks of not less than 16.7 mmol/L,the models were considered successful.40 rats with type 2 diabetes mellitus were randomly divided into 4 groups(n=10 each)using a random number table: sham operation group(group Sham),myocardial ischemia/reperfusion group(group I/R),myocardial ischemia/reperfusion with sevoflurane postconditioning group(group SP),myocardial ischemia/reperfusion with sevoflurane postconditioning and inhibitor Mdivi-1 group(group M-SP).Myocardial I/R was induced by occluding the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion except for group Sham.Sevoflurane was inhaled for 5 min at the beginning of reperfusion in group SP and group M-SP;In group M-SP,intravenous injection of Mdivi-11.2 mg/kg 15 min before ischemia.Drawing blood in the right internal jugular vein at 120 min of reperfusion,then take serum after high speed centrifugation,measuring the concentration of cTnI by ELISA.Next,rats were sacrificed and cardiac tissues were obtained.myocardial infarct size(IS)and area at risk(AAR)were determined by TTC staining,Cardiomyocyte apoptosis index(AI)were calculated by TUNEL,the expression of activated caspase-3 at protein levels were determined by western blot.Results:1.Results of AAR and IS.Compared with group Sham,in other groups,AAR were increased significantly(P < 0.01),but no statistically significant difference in AAR between the 3 groups(P>0.05).Compared with group Sham,in other groups,IS were increased significantly(P<0.05);Compared with group I/R,IS were decreased in group M-SP(P<0.05),while no significant change was found in group SP(P>0.05);Compared with group SP,IS were decreased in group M-SP(P<0.05).2.Concentration of cTnI.Compared with group Sham,in other groups,cTnI were increased significantly(P<0.05);Compared with group I/R,cTnI were decreased in group M-SP(P<0.05),while no significant change was found in group SP(P>0.05);Compared with group SP,cTnI were decreased in group M-SP(P<0.05).3.Results of TUNEL.Compared with group Sham,in other groups,AI were increased significantly(P<0.05);Compared with group I/R,AI were decreased in group M-SP(P<0.05),while no significant change was found in group SP(P>0.05);Compared with group SP,AI were decreased in group M-SP(P<0.05).4.Results of western blot.Compared with group Sham,in other groups,the expression of activated caspase-3 was increased significantly(P<0.05);Compared with group I/R,the expression of activated caspase-3 was decreased in group M-SP(P<0.05),while no significant change was found in group SP(P>0.05);Compared with group SP,the expression of activated caspase-3 was decreased in group M-SP(P<0.05).Conclusion:Sevoflurane postconditioning-induced myocardial protection of rats could be abolished under diabetic conditions.While this protection effect could be restored if Drp1 activity was inhibited,it means that Drp1 activity was related to the mechanism.