Role of PI3K-Akt-eNOS signaling pathway in attenuation of myocardial ischemia-reperfusion injury by sevoflurane postconditioning in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of PI3-kinase-Akt-endothelial nitric oxide synthase (PI3KAkt-eNOS) signaling pathway in the attenuation of myocardial ischemia-reperfusion (I/R) injury by sevoflurane postconditioning in rats.Methods Fifty healthy male Wistar rats weighing 250-280 g aged 2-3 months were randomly divided into 5 groups ( n =10 each)sham operation group (group S),I/R group,sevoflurane postconditioning group (group Spo),sevoflurane postconditioning + dimethyl sulfoxide (DMSO) group (group Spo + D),and sevoflurane postconditioning + LY294002 (a specific PI3K inhibitor) group (group Spo+ L).I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion in anesthetized rats.In group Spo,sevoflurane was inhaled for 5 min after the end-tidal concentration reached 2.5％-3.0％ at 1 min before reperfusion.In group Spo + L,LY294002 0.3 mg/kg in 0.02％ DMSO was injected intravenously at 5 min before reperfusion,and then sevoflurane postconditioning was performed.In group Spo + D,0.02％ DMSO equal to the volume of LY294002 was injected intravenously at 5 min before reperfusion,and then sevoflurane postconditioning was performed.Arterial blood samples were taken at 120 min of reperfusion for determination of the levels of creatine kinase isoenzyme MB (CK-MB),lactate dehydrogenase (LDH) and cardiac Troponin Ⅰ (cTnI).The myocardial infarct size (IS) and area at risk (AAR) were measured and IS/AAR ratio was calculated.The rats were sacrificed at 120 min of reperfusion and the myocardial tissues in the area at risk were taken for determination of the expression of Akt,phosphorylated Akt (p-Akt),eNOS and phosphorylated eNOS (peNOS) by Western blot.The ratios of p-Akt/Akt and p-eNOS/eNOS were calculated.Results Compared with group S,the levels of CK-MB,LDH and cTnI,IS/AAR ratio,p-Akt/Akt ratio and p-eNOS/eNOS ratio were significantly increased in the other groups ( P ＜ 0.05 or 0.01 ).Compared with group I/R,no significant change was found in the parameters mentioned above in group Spo+ L (P ＞ 0.05),and the levels of CK-MB,LDH and cTnI and IS/AAR ratio were significantly decreased,and the ratios of p-Akt/Akt and p-eNOS/eNOS were significantly increased in groups Spo and Spo + D ( P ＜ 0.05 or 0.01 ).There was no significant difference in the parameters mentioned above between group Spo and group Spo + D (P ＞ 0.05).Conclusion PI3K-Akt-eNOS signaling pathway mediates the attenuation of myocardial I/R injury by sevoflurane postconditioning in rats.