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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 explore the protective effect of Huangqi San on cardiomyopathy in experimental type 2 diabetic rats and its mechanism. Methods: Thirty - six male Sprague Dawley rats were randomly divided into 4 groups: normal group, model group, astragalus group (2.4 g · kg -1) and losartan group (0.1 g · kg -1 )). Cardiomyopathy model rats with type 2 diabetes mellitus were reproduced by intraperitoneal injection of high fat diet and streptozocin (STZ). The rats were administered intragastrically for 16 weeks. The effects of Astragalus membranaceus on the fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), myocardial morphology, collagen changes, The effect of Mitsugumin 53 (MG53) and peroxisome proliferator-activatedactivated receptor-α (PPAR-α) mRNA expression was detected by Real-time PCR. Results: Compared with normal group, the content of FBG, TC, TG, HDL-C and LDL-C in model group were significantly increased (P <0.01), and the myocardial tissue was disordered and uneven in size. The deposition of vacuoles and the interval between muscle fibers were obviously widened. The collagen fibers accumulated in the interstitial and perivascular area of muscle cells, and the relative content of collagen in muscle tissue was significantly increased (P <0.01), while the expressions of myocardial MG53 and PPAR-α mRNA were increased. Compared with the model group, the Astragalus membranaceus group could obviously reduce the level of blood glucose and blood lipid (P <0.05, P <0.01). The Astragalus mongholicus group showed regular arrangement of muscle fibers, no fat deposits and no fibrinolysis (P <0.05, P <0.01). The expression of MG53 and PPAR-α mRNA in the Astragalus mongholicus group was obviously decreased (P <0.05). CONCLUSION: Astragalus may play a preventive and therapeutic role in the pathogenesis of diabetic cardiomyopathy. Its mechanism is to inhibit the expression of MG53 and PPAR-α mRNA by improving the blood glucose and lipid levels and regulating the MG53 / PPAR-α pathway.