Role of signal transducer and activator of transcription 3 signaling pathway in reduction of myocardial ischemia-reperfusion injury by diazoxide postconditioning in rats

Abstract

Objective To evaluate the role of signal transducer and activator of transcription 3 (STAT3) signaling pathway in the reduction of myocardial ischemia-reperfusion (I/R) injury by diazoxide postconditioning in rats.Methods Sixty adult male Sprague-Dawley rats,aged 3 months,weighing 240-260 g,were randomly divided into 5 groups (n =12 each):sham operation group (S group),I/R group,vehicle group (V group),diazoxide postconditioning group (D group),and STAT3 signaling pathway inhibitor Stattic group (St group).Myocardial I/R was produced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.In V and D groups,0.4％ dimethyl sulfoxide and 7 mg/kg diazoxide (in 1 ml of 0.4％ dimethyl sulfoxide) were injected through the femoral vein at the onset of reperfnsion,respetively.In St group,Stattic was injected through the femoral vein 10 min before reperfusion,and the other procedures were the same as those in D group.The infarct size (IS) and myocardial apoptosis were detected by TTC staining and TUNEL,respectively.Apoptotic index (AI) was calculated.STAT3 mRNA expression in myocardial tissues was detected using RT-PCR.Western blot was used to detect the phosphorylation of STAT3.Results Compared with S group,the IS and AI were significantly increased and the expression of STAT3 mRNA and phosphorylation of STAT3 were decreased in I/R group (P ＜ 0.05).Compared with I/R group,the IS and AI were significantly decreased and the expression of STAT3 mRNA and phosphorylation of STAT3 were increased in D group (P ＜ 0.05).There was no significant difference in IS,AI,expression of STAT3 mRNA and phosphorylation of STAT3 between V group and St group (P ＞0.05).Compared with group D,the IS and AI were significantly increased and the expression of STAT3 mRNA and phosphorylation of STAT3 were decreased in St group (P ＜ 0.05).Conclusion STAT3 signaling pathway is involved in the reduction of myocardial I/R injury by diazoxide postconditioning in rats. Key words: STAT3 transcription factor; Diazoxide ; Myocardial reperfusion injury; Apoptosis