Mechanism of protective effect of hydromorphone postconditioning on myocardium in rats: PI3K/Akt signaling pathway-mediated autophagy / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the relationship between the mechanism of protective effect of hydromorphone postconditioning on myocardium and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway-mediated autophagy in rats.Methods:Forty healthy male Sprague-Dawley rats, weighing 220-250 g, were divided into 5 groups ( n=8 each) using a random number table method: sham operation group (Sham group), ischemia-reperfusion (I/R) group (group IR), hydromorphone postconditioning group (group HP), PI3K inhibitor group (group W) and hydromorphone postconditioning+ PI3K inhibitor group (group HP+ W). Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.In group HP, hydromorphone 0.1 mg/kg was injected via femoral vein at 5 min before reperfusion in group HP.In group HP+ W, hydromorphone 0.1 mg/kg and wortmannin (PI3K inhibitor) 15 μg/kg were injected via femoral vein at 5 min before reperfusion.In group W, wortmannin 15 μg/kg was injected via femoral vein at 5 min before reperfusion.At the end of reperfusion, the myocardial infarct size (IS) was determined by TTC staining, the activities of serum lactate dehydrogenase (LDH) was detected by colorimetry, myocardial specimens were collected for microscopic examination of the ultrastructure (with a electron microscope), the expression of phosphorylated Akt (p-Akt) and microtubule-associated protein 1 light chain 3 (LC3) was determined by Western blot and the ratio of LC3-Ⅱ/Ⅰwas calculated. Results:Compared with Sham group, IS and the activities of serum of LDH were significantly increased, p-Akt expression in myocardial tissues was up-regulated, the ratio of LC3-Ⅱ/Ⅰwas increased ( P<0.05), autophagic vacuoles were increased and the damage of ultrastructure of cardiomyocytes was obvious in group IR.Compared with group IR, IS and the activities of serum of LDH were significantly decreased, p-Akt expression in myocardial tissues was up-regulated, the ratio of LC3-Ⅱ/Ⅰwas decreased ( P<0.05), autophagic vacuoles were decreased and the damage of ultrastructure of cardiomyocytes was attenuated in group HR.Compared with group HR, IS and the activities of serum of LDH were significantly increased, p-Akt expression in myocardial tissues was down-regulated, the ratio of LC3-Ⅱ/Ⅰwas increased ( P<0.05), autophagic vacuoles were increased and the damage of ultrastructure of cardiomyocytes was aggravated in group HR+ W. Conclusion:The mechanism of protective effect of hydromorphone postconditioning on myocardium is related to activation of PI3K/Akt signaling pathway and inhibition of autophagy in rats.