The role of PI3K-Akt signal pathway in protection of myocardium agalnst ischemia-reperfusion injury by diazoxide postconditioning in rats

Abstract

Objective To investigate the role of phosphatidylinositol 3-kinase/protein-serine-threonine ki- nases （PI3K-Akt） signal pathway in the protection of myocardium against ischemia-repeffusion （I/R） injury by diazoxide postconditioning in rats. Methods Thirty-six male SD rats weighing 250-300 g were randomly divided into 4 groups using random number table （ n = 9 each） ： group I/R; group diazoxide （group D） ; group wortmannin （ PI3K inhibitor） （group W） and group wortmannin ＋ diazoxide （group WD）. The animals were anesthetized with intraperitoneal 10% chloral hydrate 4 ml/kg, intubated and mechanically ventilated. Myocardial I/R was produced by 30 min occlusion of left anterior descending coronary artery followed by 120 rain repeffusion. 0.1% dimethyl sulfoxide （the vehicle for diazoxide and wortmannin ）/diazoxide at 0.47 mg. kg-1 . min-I/wortmannin at 1 μg.kg-1 .min-1 was infused for 15 rain starting from 25 min of isehemia in groups I/R,D and W respectively. In group DW wortmannin was infused at 5 rain before diazoxide infusion. Blood samples were collected from left ventricle at the end of 120 min repeffusion for measurement of lactate dehydrogenase （LDH） activity. Myocardial in-farct size was measured. Myocardial specimens were obtained for determination of apoptosis index （the number of apoptotic cells/the total number of ceils examined） and expression of Bcl-2 and Bax. Bcl-2/Bax ratio was calculat- ed. Results Diazoxide postconditioning significantly decreased plasma LDH activity, myocardial infarct size, apoptosis index and Bax expression in myocardium and increased myocardial Bcl-2 expression and Bcl-2JBax ratio in group D compared with group I/R. Wortmannin partly counteracted the protective effects of diazoxide postconditioning against myocardiul infarct. There was no significant difference in the above variables between groups I/R and W. Conclusion PI3K-Akt signal pathway is involved in the protective effects of diazoxide postconditioning on myocardium against I/R injury. Key words: 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; Diazoxide; Myocardial reperfusion injury