Role Of PI3K-Akt Pathway In Sevoflurane Postconditioning-induced Mitigation Of Myocardial Ischemia-reperfusion Injury Via Up-regulation Of Heme Oxygenase-1 Expression In Rats

Objective:To determine the effect of sevoflurane postconditioning on the expression of heme oxygenase-1(HO-1)in myocardium of rats with myocardial ischemia-reperfusion injury(MIRI)and the role of PI3K-AKT signaling pathway.Methods:In the experiment,thirty male Sprague-Dawley rats weighing 230~280g were randomly assigned into five separate groups(n=6): Sham group(group S),Myocardial ischemia-reperfusion injury group(group I/R),Sevoflurane postconditioning group(group Se),Sevoflurane postconditioning + Wortmannin group(group Se+W)and Wortmannin group(group W).Group S was receieved no occlusion or reperfusion.In gronp I/R,group Se,group Se+W and group W,the myocardial ischemia-reperfusion injury(MIRI)model was produced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.In groups Se and Se+W,rats with myocardial ischemia inhaled 1.0 minimum alveolar concentration(MAC)sevoflurane for5 min at the 1 min before reperfusion.Wortmannin(15?g/kg)were injected intravenously at 5 min before reperfusion in groups Se+W and W,rats in group I/R and group Se were given the corresponding volume of saline.After 120 min reperfusion,the rats arterial blood and myocardial tissues were taken for the analysis of experimental results.(1)Drawing blood from abdominal aorta to determine the cTnI level by Elisamethod.(2)The content of MDA was determined by thiobarbituric acid coloration method,and the activity of SOD was determined by purine oxidase method.(3)The expression of Akt,p-Akt and HO-1 protein was measured by Western blotting and the ratio of p-Akt/Akt was calculated.Results:Compared with the group S,the serum cTnI and myocardial MDA contentration,the expression of HO-1 and p-Akt and the ratio of p-Akt?Akt were increased obviously,and the SOD activity decreased clearly in the other groups.P<0.05 was considered statistically significant.Compared with group I/R,the content of cTnI in serum and the content of MDA in myocardium were decreased,while the expression of HO-1 and p-Akt,the ratio of p-Akt?Akt and the SOD activity in myocardium were increased in the group Se(P<0.05).Compared with group Se,the content of serum cTnI and the content of MDA in myocardium were increased in groups Se+W and W,and the expression of HO-1 and p-Akt was decreased,the ratio of p-Akt?Akt was decreased,the SOD activity in myocardial tissue decreased obviously,the difference was statistically significant(P<0.05).Conclusion:Sevoflurane postconditioning exerted a protective effect against myocardial ischemia-reperfusion injury by up-regulation the expression of HO-1.The mechanism may be connected to the PI3K-Akt pathway.