Effect of oxycodone pretreatment on myocardial ischemia-reperfusion injury in rats and its relationship with PI3K/Akt signaling pathway

Objective To evaluate the effect of oxycodone pretreatment on myocardial ischemia-reperfusion(I/R)injury in rats and its relationship with phosphatidylinositol 3-kinase/serine-threonine kinase(PI3K/Akt)signaling pathway. Methods Forty-eight healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 250-320 g, were randomly divided into 4 groups(n=12 each)using a random number table: sham operation group(group S); group I/R; oxycodone pretreatment group(group OP); LY204002(PI3K/Akt signaling pathway blocker)group(group LY). Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery, followed by 120 min reperfusion in I/R, OP and LY groups.In group S, the anterior descending branch was only exposed but not ligated.Oxycodone injection 0.5 mg/kg was injected via the internal jugular vein at 5 min before reperfusion in OP and LY groups, respectively, while the equal volume of normal saline was injected via the internal jugular vein at 5 min before reperfusion in S and I/R groups.LY294002 1.4 mg/kg was injected intraperitoneally at 30 min before oxycodone administration in group LY.At 120 min of reperfusion, blood samples were collected from the hearts for determination of creatine kinase-MB(CK-MB)and cardiac troponin I(cTnI)concentrations in serum.The animals were then sacrificed, and myocardial specimens were obtained for measurement of myocardial infarct size(IS), for examination of pathological changes(with light microscope), and for determination of the expression of Bcl-2 and Bax(by immunohistochemistry). Bcl-2/Bax ratio was calculated. Results Compared with group S, the serum CK-MB and cTnI concentrations were significantly increased, the myocardial IS was significantly increased, the expression of Bcl-2 and Bax was significantly up-regulated, and the Bcl-2/Bax ratio was significantly decreased in I/R, OP and LY groups(P<0.05). Compared with group I/R, the serum CK-MB and cTnI concentrations were significantly decreased, the myocardial IS was significantly decreased, Bcl-2 expression was significantly up-regulated, Bax expression was significantly down-regulated, the Bcl-2/Bax ratio was significantly increased(P<0.05), and the pathological changes were attenuated in OP and LY groups.Compared with group OP, the serum CK-MB and cTnI concentrations were significantly increased, the myocardial IS was significantly increased, Bcl-2 expression was significantly down-regulated, Bax expression was significantly up-regulated, the Bcl-2/Bax ratio was significantly decreased(P<0.05), and the pathological changes were aggravated in group LY. Conclusion Oxycodone pretreatment can mitigate myocardial I/R injury in rats, and the mechanism is associated with activation of PI3K/Akt signaling pathway and inhibition of apoptosis in cardiomyocytes. Key words: Oxycodone; Myocardial reperfusion injury; 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases