Study On The Mechanism Of Sevoflurane Postconditioning Improving Mitochondrial Respiratory Function To Reduce Myocardial Ischemia-reperfusion Injury In Rats

Objective: To investigate whether Sevoflurane postconditioning improves myocardial mitochondrial respiratory function and mitochondrial respiratory enzyme activity and reduces myocardial ischemia-reperfusion injury by regulating hypoxia-inducible factor-1?.Methods: The myocardial ischemia-reperfusion rat model was established using the Langendorff isolated heart perfusion apparatus.A total of 88 healthy adult male Sprague-Dawley(SD)rats were randomly divided into 4 groups(n=22)as follows: normal control(C)group,ischemia-reperfusion(I/R)group,SPostC group,and HIF-1? inhibitor(2-methoxyestradiol,2ME2)+ SPostC(MSP)group.The C group received persistent perfusion of Krebs-Henseleit(K-H)solution for 180 min.The I/R group was equilibrated for 20 min,followed by perfusion of 4°C St.Thomas cardioplegia;and then,whole heart ischemia was performed at 32°C for 40 min.afterwards,the rats were perfused with K-H solution for 120 min,The SPostC group was equilibrated for 20 min,followed by perfusion of 4°C St.Thomas cardioplegia.and then,whole heart ischemia was performed for 40 min at 32°C,Afterwards,the rats were perfused with 1.0 MAC(minimum alveolar concentration)of sevoflurane-saturated K-H solution for 15 min,followed by continuous perfusion of K-H solution for 105 min.The MSP group was perfused with 2ME2(2 ?M)+ 1.0 MAC of saturated K-H solution for 15 min after 40 min of whole heart ischemia followed by continuous perfusion of K-H solution for 105 min.The hemodynamic parameters were recorded at the end of balance(T1)and the end of the reperfusion(T2).Myocardial mitochondrial respiratory state 3(State3),respiratory control ratio(Respiratory Control Ratio,RCR)and nicotinamide adenine dinucleotide oxidase(NADH-OX),succinate oxidase(Suc-OX)cytochrome C oxidase(Cytc-OX)and other enzyme activity were measured by the oxygen electrode.The changes of ultrastructure of cardiomyocytes were observed by transmission electron microscope.The myocardial mitochondrial ROS production rate was measured using fluorescence Spectrometry.Detection of HIF-1 alpha protein levels.Results:Compared to the ischemia-reperfusion(I/R)group,HIF-1? expression in the SPostC group was significantly up-regulated.Additionally,cardiac function indicators,mitochondrial state 3 respiratory rate,respiratory control ratio(RCR),cytochrome C oxidase(CcO),NADH oxidase(NADHO),and succinate oxidase(SUCO)activities,mitochondrial ROS production rate,and mitochondrial ultrastructure were significantly better than those in the I/R group.However,these advantages were completely reversed by the HIF-1? specific inhibitor 2ME2(P<0.05).Conclusion: The myocardial protective function of SPostC might be associated with the improvement of mitochondrial respiratory function after up-regulation of HIF-1?expression...