Effects of Autophagy and PI3K-Akt Pathway in Sufentanil Postconditioning on Myocardial Ischemia-reperfusion Injury Protection
Wang Zhihua
Tian Shouyuan
Wang Jiangang
He Xuan
Zhu Jian
Abstract：Objective To investigate the roles of autophagy and PI3K-Akt signaling pathway on sufentanil postconditioning-mediated alleviation of myocardial ischemia-reperfusion injury (MIRI). Methods Thirty -five male Sprague-Dawley (SD)rats weighed 220 g to 260 g were randomly divided into five groups (n=7 each):Sham operation group (group S),ischemia-reperfusion group (group I/R),Sufentanil postconditioning group (group SP),sufentanil postconditioning plus Wortmannin (a specific PI3K inhibitor) group (group SP+W)and Wortmannin group (group W).In groups I/R,SP,SP+W and W,the myocardial I/R models were prepared by 30 min ligation of left anterior descending coronary artery(LAD)followed by 120 min reperfusion. Group S underwent the operation with a stitch placed around but not ligating the artery.In groups I/R,SP,SP+W and W rats were treated with 1 mL normal saline,1μg/kg sufentanil,1μg/kg sufentanil plus 15μg/kg wortmannin and 15μg/kg wortmannin intravenous infusion via the femoral vein for 5 min prior to reperfusion,respectively. Abdominal aortic blood samples were collected at 120 min of reperfusion for measurement of the se-rum creatine kinase-MB (CK-MB)concentration. The cardiac apexes were collected after executed the rats.The expression of Akt, phosphorylated-Akt (p -Akt)and LC3-Ⅱ were detected by Western blotting and the formation of autophagy was observed by elec-tron microscope.Results Compared with group S,the concentration of CK-MB and the expression of LC3-Ⅱ increased in groups I/R,SP,SP+W and W,the ratio of p-Akt/Akt higher in groups I/R,SP,SP+W and W (P<0.05)and the formation of autophagy was increased. Compared with group I/R,the concentration of CK-MB and the expression of LC3-Ⅱ decreased in group SP,the ratio of p-Akt/Akt higher in group SP (P<0.05)and the formation of autophagy was decreased. Compared with group SP,the concentration of CK-MB and the expression of LC3-Ⅱ increased in groups SP+W and W,the ratio of p-Akt/Akt lower in groups SP+W and W (P<0.05)and the formation of autophagy was increased.Conclusion Sufentanil postprocessing through inhibition of autophagy in myocardial ischemia reperfusion injury play a protective role,including PI3K-Akt pathway may be one of the main mechanisms.
Keywords：myocardial ischemia-reperfusion injuryautophagysufentanilPI3K-Akt pathway
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 415-418 )