黄芪散对2型糖尿病大鼠心肌MG53/PPAR-α通路的影响

Effect of Huangqi San on MG53/PPAR-α Pathway in Type 2 Diabetes Mellitus Cardiomyopathy Rats

目的:探索黄芪散对实验性2型糖尿病大鼠心肌病变的保护作用及作用机制。方法:36只雄性SD大鼠随机分为4组,分别为正常组,模型组,黄芪散组(2.4 g·kg^(-1))和氯沙坦组(0.1 g·kg^(-1))。采用高脂饲料喂养和链脲佐菌素(streptozocin,STZ)腹腔注射的方法复制2型糖尿病大鼠心肌病变模型,连续灌胃给药16周,观察黄芪散对各组大鼠血清中空腹血糖(FBG),总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C),心肌形态学、胶原纤维变化,实时荧光定量聚合酶链式反应(Real-time PCR)检测Mitsugumin 53(MG53)及过氧化物酶体增殖物激活受体-α(peroxisome prolifer-ationactivated receptor-α,PPAR-α)mRNA表达的影响。结果:与正常组比较,模型组大鼠FBG,TC,TG,HDL-C,LDL-C含量均显著升高(P<0.01),心肌组织排列紊乱,大小不均匀,肌纤维间可见明显的脂肪空泡沉积,肌纤维间隔明显增宽,肌细胞间质、血管周围可见胶原纤维堆积,且肌组织胶原相对含量明显增加(P<0.01),心肌MG53,PPAR-α mRNA表达有所升高;与模型组比较,黄芪散组可以明显降低血糖、血脂含量(P<0.05,P<0.01),黄芪散组大鼠表现出肌纤维排列规则,纤维间未见脂肪沉积,也未见纤维溶解等,并可明显抑制心肌胶原纤维增生;黄芪散组可显著降低MG53,PPAR-α mRNA的表达(P<0.05,P<0.01)。结论:黄芪散对实验性糖尿病心肌病变具有一定的防治作用,其作用机制是通过改善血糖、血脂水平,调控MG53/PPAR-α通路,抑制MG53,PPAR-α mRNA的表达。

Objective： To study the protective effect of Huangqisan（ HQS） on cardiomyopathy of rats with type 2 diabetes mellitus（ T2DM） and its mechanism. Method： Thirty-six male SD rats were randomized into4 groups,namely normal group,model group,HQS group（ 2. 4 g·kg^-1）,and Losartan treatment group（ 0. 1 g·kg^-1）,with 12 rats in each group. Rats received high fat diet and streptozocin（ STZ） to reproduce the model of type 2 diabetic cardiomyopathy rats,and were orally administered with drugs for 16 consecutive weeks. Fasting blood glucose（ FBG）,total cholesterol（ TC）,triglyceride（ TG）,high density lipoprotein cholesterol（ HDLC）, low density lipoprotein cholesterol（ LDL-C） and histological features of myocardium were observed.Mitsugumin 53（ MG53） and peroxisome proliferator-activated receptor-α（ PPAR-α） mRNA expression were observed by Real-time PCR. Result： Compared with the normal group,the levels of FBG,TC,TG,HDL-C,LDL-C and MG53,PPAR-α mRNA expression in model groups were significantly elevated（ P〈0. 01）. Besides,disordered arrangement and different sizes of myocardial tissues,obvious fat vacuole and widened interval between fibers were found in the model group. Compared with the model group,the levels of FBG,TC,TG,HDL-C and LDL-C in HQS group were significantly reduced（ P〈0. 05,P〈0. 01）. Both of HQS group showedregular myocardial tissue,without fat vacuole and fiber dissolution. But HQS group showed scanty fat vacuole in fiber interval. HQS group showed significant reduction in MG53,PPAR-α mRNA expressions（ P〈0. 05,P〈0. 01）.Conclusion： HQS has a good therapeutic effect on diabetic cardiomyopathy rats. Its mechanism may be related to reduction in the level of blood glucose and blood lipids,regulation on MG53 / PPAR-α signaling pathway and inhibition of MG53,PPAR-α mRNA expressions of myocardium.