Role Of Nitric Oxide In Sevoflurane Postconditioning Induced Amelioration Of Ischemia-reperfusion Autophagy And Apoptosis In Isolated Rat Hearts

Objective:To discuss the role of nitric oxide in sevoflurane postconditioning induced amelioration of autophagy and apoptosis in isolated ischemia/reperfusion(I/R) rat hearts Methods:Male Sprague-Dawley rats hearts were isolated, linked to Langendorff perfusion apparatus, equally and randomly divided into 6 groups(n=19): SHAM group, SEVO group, I/R group, SEVOP group, SEVOP+L group, L-NAME group. With the exception of SHAM group and SEVO group, each group was subjected to occlusion for 30 min followed by reperfusion for 120 min. In SEVO group, 3% sevoflurane was administered at the sixth minute of perfusion for 15 min. 3% sevoflurane and L-NAME(100 μmol/L) were administered at the onset of reperfusion in SEVOP group and L-NAME group for 15 min and 60 min respectively. In SEVOP+L group, both 3% sevoflurane and L-NAME were administered at the onset of reperfusion. At the end of experiment, the infarct size was measured by triphenyltetrazoliumchloride(TTC) staining method and nitric oxide(NO)concent as well as the activity of NOS were measured. The formation of autophagosomes was observed by transmission electron microscope(TEM). The expressions of proteins(Beclin 1、Bcl-2 �'� Caspase-3) were measured at the end of 2-h reperfusion. Results:After experiencing myocardial ischemia-reperfusion injury, infarct size was increased, myocardial NO concent and the activity of NOS were decreased, the expression of Bcl-2 was down-regulated, the expressions of Beclin 1 and Caspase-3 were up-regulated(P < 0.05). sevoflurane decreased infarct size, increased myocardial NO concent and the activity of NOS, up-regulated the expression of Bcl-2 and down-regulated the expressions of Beclin 1 and Caspase-3(P < 0.05). But these effects abolished by NOS inhibitor L-NAME. Conclusion:Sevoflurane postconditioning ameliorate myocardial I/R injury and the underlying mechanism may be related to increase NO concent, up-regulation of the expression of Bcl-2, thereby inhibit autophagy and apoptosis during reperfusion.