人参皂苷Rb1通过上调PGC-1α缓解糖尿病心肌病

目的:研究人参皂苷Rb1对糖尿病心肌病的治疗作用并阐明其分子机制。方法:采用腹腔注射链脲佐菌素的方法,建立糖尿病心肌病动物模型。将小鼠分为3组:WT组,DM组,DM+Rb1组。超声心动图分析小鼠心功能;Western blot分析PGC-1α、cleaved caspase-3、bcl-2等蛋白表达;MitoSOX染色分析线粒体ROS含量;透射电镜分析线粒体数目。结果:与WT组相比,DM组小鼠心功能显著下降(LVEF,P<0.01),PGC-1α表达下调(P<0.01),线粒体数目减少(P<0.01);而Rb1处理后,显著改善了DM小鼠心功能(LVEF,P<0.01),恢复了PGC-1α表达(P<0.05),增加了线粒体数目(P<0.05)。同时,Rb1处理后,减少了糖尿病小鼠心肌线粒体ROS产生(P<0.01),恢复了bcl-2蛋白表达(P<0.01),降低了cleaved caspase-3蛋白表达(P<0.01),从而减少了高糖引起的细胞凋亡(P<0.05)。而siPGC-1α处理后,阻断了Rb1的上述作用。结论:人参皂苷Rb1通过上调PGC-1α改善糖尿病小鼠心功能,缓解糖尿病心肌病。其机制可能与人参皂苷Rb1降低心肌线粒体ROS产生并减少心肌细胞凋亡有关。

Ginsenoside Rb1 Alleviates Diabetic Cardiomyopathy through Up-regulating PGC-1α

Objective:To study the therapeutic effect of ginsenoside Rb1 on diabetic cardiomyopathy and to elucidate its molecular mechanism.Methods:An animal model of diabetic cardiomyopathy was established by intraperitoneal injection of streptozotocin.Mice were divided into 3 groups:WT group,DM group and DM+Rb1 group.Cardiac function of mice was analyzed by echocardiography.Expression of PGC-1α,cleaved caspase-3 and bcl-2 was analyzed by Western blot.Mitochondrial ROS content was analyzed by MitoSOX staining.The number of mitochondria was analyzed by electron microscopy.Results:Compared with the WT group,the cardiac function of the DM group was significantly decreased(LVEF,P<0.01).Expression of PGC-1αwas down-regulated(P<0.01).The number of mitochondria was decreased(P<0.01).After Rb1 treatment,the cardiac function of DM mice was significantly improved(LVEF,P<0.01).PGC-1αexpression was restored(P<0.05).The number of mitochondria was increased(P<0.05).At the same time,Rb1 treatment reduced myocardial mitochondrial ROS production(P<0.01),restored bcl-2 protein expression(P<0.01),decreased cleaved caspase-3 protein expression(P<0.01),and decreased Apoptosis induced by high glucose(P<0.05).After treatment with siPGC-1α,the above protective effects of Rb1 were blocked.Conclusions:Ginsenoside Rb1 improves cardiac function and alleviates diabetic cardiomyopathy by up-regulating PGC-1α.The mechanism may be related to the reduction of myocardial mitochondrial ROS production and reduction of cardiomyocyte apoptosis by ginsenoside Rb1.