白藜芦醇通过激活腺苷酸活化蛋白激酶预防酒精性心肌病

Resveratrol Prevents Alcoholic Cardiomyopathy Through Activating AMP-Activated Protein Kinase

目的探索白藜芦醇对酒精性心肌病的作用及其分子机制。方法将雄性Wistar大鼠随机分为对照组、酒精组和酒精+白藜芦醇组,每组10只,干预6个月后采用介入生理记录仪检测大鼠的心功能,采用常规石蜡切片和HE染色法评估心脏结构改变,采用免疫印迹法检测心肌组织中腺苷酸活化蛋白激酶和内皮型一氧化氮合酶及其磷酸化蛋白的表达,并运用硝酸还原酶法检测心肌组织中一氧化氮水平。结果 6个月酒精摄入可显著损害大鼠的心功能和心肌显微结构,添加白藜芦醇能显著削弱酒精对心脏功能和结构的损害作用。酒精摄入可显著降低心肌组织中腺苷酸活化蛋白激酶和内皮型一氧化氮合酶的磷酸化水平,并降低一氧化氮水平,而添加白藜芦醇能显著增加腺苷酸活化蛋白激酶和内皮型一氧化氮合酶的磷酸化水平,并增加心肌组织中一氧化氮水平。结论白藜芦醇能通过激活腺苷酸活化蛋白激酶/内皮型一氧化氮合酶系统和增加一氧化氮水平来预防酒精性心肌病。

Aim To investigate the effect of resveratrol on alcoholic cardiomyopathy and the underlying molecular mechanisms. Methods Male Wistar rats were divided into three groups： control,alcoholic,and alcoholic plus resveratrol group,n=10 for each group.After the intervention for six months,the invasive cardiac function of the rats was measured by physiological recorder,the histological structure of heart was evaluated by HE staining,the expression and phosphorylation of AMP-activated protein kinase（AMPK） and endothelial nitric oxide synthase（eNOS） in myocardium were determined by western blot,and the nitric oxide（NO） level in myocardium was detected by nitrate reductase method. Results Alcoholic intake for six months caused a significant decline in cardiac function and an obvious damage in cardiac structure.Oral administration with resveratrol partially reversed alcoholic-induced cardiac damage.Alcoholic intake significantly decreased the phosphorylated level of AMPK and eNOS and consequently decreased the NO level in myocardium.Treatment with resveratrol remarkably attenuated alcoholic-induced decline in the phosphorylation of AMPK and eNOS and decrease in NO level. Conclusion Resveratrol activates AMPK/eNOS pathway,increases NO level,and consequently prevents alcoholic cardiomyopathy.