Role of silent information regulator 1 in ischemic preconditioning-induced alleviation of myocardial ischemia-reperfusion injury

Objective To evaluate the role of silent information regulator 1 (SIRT1) in ischemic preconditioning (IPC)-induced alleviation of myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty-eight male Sprague-Dawley rats,aged 12 weeks,weighing 200-250 g,were randomly divided into 4 groups (n =12 each):sham operation group (S group),I/R group,IPC group and IPC + SIRT1 inhibitor ex527 group (IPC + ex527 group).Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion.IPC was induced by 3 episodes of 5 min occlusion of left anterior descending branch at 5 min intervals before myocardial ischemia.SIRT1 inhibitor ex527 1 μg/kg was injected intravenously 15 min before myocardial ischemia and at 1 min before reperfusion.Blood samples were collected before myocardial ischemia and at 120 min of reperfusion for measurement of serum TNF-α and IL-6 concentrations by ELISA.The rats were then sacrificed and myocardial specimens were obtained for determination of myocardial lactic dehydrogenase (LDH) and creatine kinase MB (CK-MB) activities,SIRT1 expression and acetylation of NF-κB p65.Results Compared with S group,the serum TNF-α and IL-6 concentrations at 120 min of reperfusion,and myocardial LDH and CK-MB activities and acetylation of NF-κB p65 were significantly increased,and SIRT1 expression was down-regulated in I/R and IPC + ex527 groups (P ＜ 0.05).Compared with I/R group,the serum TNF-α and IL6 concentrations at 120 min of reperfusion,and myocardial LDH and CK-MB activities and acetylation of NF-κB p65 were significantly decreased,SIRT1 expression was up-upregulated in group IPC (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group IPC + ex527 (P ＞ 0.05).Compared with IPC group,the serum TNF-α and IL-6 concentrations at 120 min of reperfusion,and myocardial LDH and CK-MB activities and acetylation of NF-κB p65 were significantly increased,and SIRT1 expression was down-regulated in group IPC + ex527 (P ＜ 0.05).Conclusion SIRT1 is involved in IPC-induced alleviation of myocardial I/R injury in rats. Key words: Sirtuins ;  NF-kappa B ;  Ischemic preconditioning, myocardial;  Myocardial reperfusion injury