白藜芦醇通过激活静息信号调节蛋白途径抑制自噬减弱心肌缺血再灌注损伤

Resveratrol protects myocardium against reperfusion injury by inhibiting autophagy through SIRT1 pathway

目的 研究白藜芦醇在离体心肌缺血再灌注损伤中的保护作用及与自噬的关系和相关通路.方法 将32只Spragur-Dawley雄性大鼠按随机数字表法分为4组,每组8只,对照组（C组）、白藜芦醇组（R组）、白藜芦醇＋尼克酰胺组（RN组）和尼克酰胺组（N组）.记录大鼠离体心脏在Langendorff灌流系统灌流稳定30min后即刻、再灌注30min及再灌注2h的血流动力学数据,并比较4组小鼠心肌梗死面积率.通过Western Blot技术及电镜观察自噬体来比较4组小鼠自噬表达水平.结果 再灌注2h后R组血流动力学数据与C组比较差异有统计学意义（P＜0.05）,R组梗死面积率与C组比较差异有统计学意义（P＜0.05）,R组自噬表达水平也明显低于C组,而这些作用在复合应用尼克酰胺后均被抑制.结论 白藜芦醇可通过激活静息信号调节蛋白途径抑制自噬的发生,从而减弱心肌缺血再灌注损伤.

Objective To investigate the effects of resveratrol on myocardial reperfusion injury and autophagy in rats. Method Thirty-two male Sprague-Dawley rats weighing 250-300 g were randomly divided into four groups （n=8 each）： group C （control）; group R （resveratrol treatment）; group RN （resveratrol ＋ nicotinamide treatment） and group N （nicotinamide treatment）. The left ventricular functional parameters were recorded at baseline, at 30min and 120min of reperfusion. The infarct size was measured after the heart was stained with triphenyltetrazolium chloride. The level of autophagy was determined by electron microscopy and Western Blot. Results The group R showed better functional parameters and smaller infarct size （16.6 ± 2.5% vs 45 ±3%） than the group C at 120min after reperfusion, while there were no differences between values of baseline and at 30min. The level of autophagy in group R was lower than that in group C. All the beneficial effects were abrogated by the SIRT1 inhibitor nicotinamide. Conclusion Resveratrol can protests myocardium from ischemia/reperfusion injury, and this protective effect may be associated with inhibition of autophagy via the SIRT1 pathway.