黄地安消胶囊抑制EndoMT干预糖尿病大血管病变的机制

Mechanism of Huangdi Anxiao(黄地安消)Capsules in Intervening T2DM Vascular Disease by EndoMT Inhibition

目的:研究内皮细胞内皮间质转化(EndoMT)在糖尿病大血管病变过程中的影响及黄地安消胶囊的干预作用。方法:采用高脂高糖饲料联合链脲佐菌素(STZ)诱导复制糖尿病大鼠模型。并将成功建模的大鼠分为模型对照组、黄地安消胶囊3、6、12 g/kg组及二甲双胍0.72 g/kg组,分别给予相应药物干预6 w。观察各组大鼠一般情况,每周测定大鼠空腹血糖(FBG);观察大鼠胸主动脉组织的病理学特征;并检测转化生长因子β1(TGF-β1)、Smad2、Smad3蛋白及mRNA、α-平滑肌肌动蛋白(α-SMA)、血管内皮钙粘蛋白(VE-cadherin)蛋白表达。结果:与正常对照组比较,模型对照组大鼠体质量明显降低(P<0.05或P<0.01),空腹血糖(FBG)显著升高(P<0.01),胸主动脉血管中TGF-β1、Smad2、Smad3蛋白及mRNA表达显著上调(P<0.01),α-SMA蛋白表达显著上调,VE-cadherin蛋白表达显著下调(P<0.01),血管内皮病理损伤严重;与模型对照组比较,黄地安消胶囊各剂量组给药第10 w后,大鼠体质量明显升高(P<0.05或P<0.01),胸主动脉血管中TGF-β1、Smad2、Smad3蛋白及mRNA表达显著下调,α-SMA蛋白表达显著下调(P<0.01),VE-cadherin蛋白表达显著上调(P<0.01),大鼠胸主动脉病理损伤减轻。结论:黄地安消胶囊可抑制TGF-β/Smad通路改善内皮间质转化(EndoMT)所致大血管病变,减轻大鼠病理损伤。

Objective:To investigate the effects of endothelial-to-mesenchymal transition(EndoMT)in the process of macrovascular lesions in diabetic vascular disease and the intervention effect of Huangdi Anxiao(黄地安消)Capsules(HDAXC).Methods:The diabetic rat model was induced by high-fat and high-sugar diet combined with streptozotocin(STZ).The successfully modeled rats were divided into HDAXC groups(3,6,and 12 g/kg)and a metformin group(0.72 g/kg),and corresponding drugs were administered for 6 weeks.The general conditions of rats in each group were observed.Fasting blood glucose(FBG)was measured weekly.Pathological characteristics of thoracic aortic tissue were observed,and the expression levels of transforming growth factorβ1(TGF-β1),Smad2,Smad3 proteins and mRNA,α-smooth muscle actin(α-SMA),and vascular endothelial cadherin(VE-cadherin)proteins were detected.Results:Compared with the normal control group,the model group showed significant decrease in body weight(P<0.05 or P<0.01),significant increase in FBG(P<0.01),significant upregulation of TGF-β1,Smad2,Smad3 proteins and mRNA in thoracic aortic blood vessels(P<0.01),significant upregulation ofα-SMA protein expression(P<0.01),significant downregulation of VE-cadherin protein expression(P<0.01),and severe vascular endothelial pathology.Compared with the results in the model control group,after 10 weeks of treatment with HDAXC at various doses,the body weight of rats significantly increased(P<0.05 or P<0.01);the expression of TGF-β1,Smad2,Smad3 proteins and mRNA in thoracic aortic blood vessels were significantly downregulated;α-SMA protein expression was significantly downregulated(P<0.01);VE-cadherin protein expression was significantly upregulated(P<0.01);the pathological damage of thoracic aorta in rats was alleviated.Conclusion:HDAXC can inhibit the TGF-β/Smad pathway to improve macrovascular lesions caused by EndoMT,thereby reducing pathological damage in rats.