It has been shown that diabetes modifies the myocardial responses to ischemia/reperfusion (I/R) and to cardioprotective agents. In this study, we aimed to investigate the effects of combined treatment with ischemic postconditioning (IPostC) and cyclosporine A (CsA) on inflammation and apoptosis of the diabetic myocardium injured by I/R. Eight weeks after induction of diabetes in Wistar rats, hearts were mounted on a Langendorff apparatus and were subsequently subjected to a 30-min regional ischemia followed by 45-min reperfusion. IPostC was induced at the onset of reperfusion, by 3 cycles of 30-s reperfusion/ischemia (R/I). The concentration of creatine kinase (CK), tumor necrosis factor (TNF)-?, interleukin (IL)-1?, and IL-6 were determined; the levels of total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3?) and B-cell lymphoma 2 (Bcl- 2) were quantified by western blotting, and the rate of apoptosis was assessed by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling (TUNEL) staining. Administration of either IPostC or CsA alone in nondiabetic animals significantly reduced CK, TNF-?, IL-1?, and IL-6 concentrations, increased the p-GSK3? and Bcl-2, and decreased the level of apoptosis (P < 0.05) but had no effect on diabetic hearts. However, in diabetic animals, after administration of CsA, the cardioprotective effects of IPostC in increasing the p-GSK3? and Bcl-2 and decreasing apoptosis and inflammation were restored in comparison with nonpostconditioned diabetic hearts. IPostC or CsA failed to affect apoptosis and inflammation and failed to protect the diabetic myocardium against I/R injury. However, combined administration of IPostC and CsA at reperfusion can protect the diabetic myocardium by decreasing the inflammatory response and apoptosis.
کلید واژگان :Diabetes . Inflammation . Apoptosis . Postconditioning . CyclosporineA . Myocardial reperfusion injury
ارزش ریالی : 600000 ریال
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