Protective effect against myocardial ischemia/reperfusion induced by diazoxide-postconditioning and its interaction with PI3K/Akt signaling pathway

Aim To explore whether the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway was involved in diazoxide-postconditioning-induced protection against cardiac ischemia/reperfusion(I/R) injury in rats.Methods 60 male SD rats were randomly divided into five groups(n=12):sham operation group(S group),I/R group,diazoxide group(D group),wortmannin group(W group) and diazoxide+wortmannin group(D+W group).Myocardial I/R model was induced in rats,and all animals were subjected to 30 min ischemia followed by 120 min reperfusion except S group.Every group was infused respectively with 0.1% DMSO,0.1% DMSO,diazoxide 7 mg·kg-1,wortmannin 15 μg·kg-1 and diazoxide 7 mg·kg-1 through the femoral vein 5 min before reperfusion,and wortmannin was given 5 min before the administration of diazoxide in D+W group.Heart rate(HR),left ventricular developed pressure(LVDP),left ventricular end-diastolic pressure(LVEDP) were recorded just before ischemia,and at the time of 30 min ischemia and 120 min reperfusion.Myocardial infarct size was measured by triphenyltetrazolium chloride(TTC) staining,TUNEL staining was used to detect apoptotic rate of myocardial cells,and the expression of p-Akt in myocardial tissue was measured with Western blot analysis at the end of reperfusion.Results There was no difference in hemodynamics(HR,LVDP,LVEDP) among different groups before ischemia(P0.05).Compared with I/R group,LVDP was increased significantly and LVEDP was decreased significantly in group D and D+W(P0.01 or 0.05);myocardial infarct size and apoptotic rate in group D and D+W were significantly reduced(P0.01 or 0.05);the expression of p-Akt in D group was increased markedly(P0.01).Compared with group D,LVDP in D+W group was significantly decreased(P0.05),the myocardial infarct size and apoptotic rate of myocardial cells in D+W group were increased markedly(P0.05),with lower expression of p-Akt(P0.01).Conclusion Diazoxide postconditioning reduces myocardial I/R injury in rats partly via activating PI3K/Akt signaling pathway.