The role of PI3/Akt signaling pathway in the protective effect of morphine postconditioning on myocardium against ischemiareperfusion injury in rats

Objective To investigate the effect of morphine postconditioning on myocardial ischemiareperfusion （I/R） injury and the role of PI3K/Akt signaling pathway in the effect. Methods Seventy male SD rats weighing280-330 g aged 16-17 weeks were randomly divided into 5 groups （n = 14 each）： group Ⅰ sham operation （S）; group Ⅱ I/R; group Ⅲ morphine postconditioning （M）; group Ⅳ morphine postconditioning ＋ wortmannin （W ＋ M） ; groupV wortmannin （W） . Myocardial I/R injury was produced by occlusion of anterior descending branch of left coronary artery for 45 min followed by 120 min reperfusion. In group M and W ＋ M （group Ⅲ, Ⅳ ） morphine 1.25 mg/kg was given iv at 3 min before and 2 min after reperfusion. In group W ＋ M and W （group Ⅳ , Ⅴ ） wortmannin （a specific PI3K inhibitor） 15μg/kg was given iv at 20 min before ischemia. The animals were sacrificed at the end of 120 rain reperfusion for assessment of ischemic and infarct area and detel Tnination of total and phosphorylated Akt expression in myocardium by Western blot. Results There were no significant differences in the size of ischemic area and total Akt expression among the 5 groups. The infarct area was significantly smaller in group M than in group I/R. The were no significant differences in the size of infarct area between group I/R, W ＋ M and W （group Ⅱ , Ⅳ, Ⅴ ）. The phosphorylated Akt expression was significantly up- regulated in group I/R and M as compared with group S, and was significantly higher in group M than in group I/R.Conclusion The PI3K/Akt signaling pathway activation is involved in the protective effect of morphine postconditioning on myocardium against I/R injury. Key words: Morphine;  Myocardial reperfusion injury;  1-Phosphatidylinositol 3-kinase;  Protein- serine-threonine kinases ;  Postconditioning