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抵当汤及其拆方对糖尿病大鼠心肌TGF-β1,TGF-β RⅡ及Smad7蛋白表达的影响
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国家自然科学基金面上项目(81273645)


Effect of Didang Tang and Its Split Recipes on Expression of Myocardium TGF-β1, TGF-β RⅡ and Smad7 in Rats with Diabetes
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    摘要:

    目的: 探讨糖尿病对大鼠心肌转化生长因子-β1(TGF-β1),转化生长因子-β受体Ⅱ(TGF-β RⅡ)及人信号转导分子7(Smad7)蛋白表达的影响及抵当汤及其拆方的干预作用。方法: 105只SD雄性大鼠单次腹腔注射链脲佐菌素(STZ)建立糖尿病模型。成模后分为模型组、抵当汤干预组、水蛭虻虫组、桃仁大黄组和缬沙坦组,以12只正常SD雄性大鼠作为正常组,分别给予相应处理。8周末,利用全自动生化仪检测空腹血糖(FBG),HE染色观察心肌病理形态学变化,Western blot法检测TGF-β1,TGF-β RⅡ及Smad7蛋白的表达。结果: 与正常组比较,模型组大鼠心肌组织细胞肥大,炎症细胞浸润较明显,心肌TGF-β1及TGF-β RⅡ蛋白表达明显升高,Smad7蛋白表达明显降低(P<0.01);与模型组比较,抵当汤可以明显减轻糖尿病大鼠心肌组织的病理改变,抵当汤明显下调大鼠心肌TGF-β1蛋白及TGF-β RⅡ蛋白表达,明显上调Smad7蛋白表达(P<0.05,P<0.01)。拆方组大鼠与糖尿病模型大鼠组比较,TGF-β1蛋白下调,心肌组织损伤也有好转,但均不如全方明显。结论: 抵当汤可减缓糖尿病大鼠心肌纤维化病变,其机制可能与下调糖尿病大鼠心肌中TGF-β1和TGF-β RⅡ蛋白表达,上调Smad7蛋白的表达有关,同时表明,抵当汤全方对DCM病变的防治作用优于拆方,"泻热化瘀通络"治法与抑制TGF-β1/Smad7信号转导通路有关。

    Abstract:

    Objective: To investigate the effect of diabetes on the expression of transforming growth factor-β1(TGF-β1), transforming growth factor-β receptors Ⅱ antibodies(TGF-β RⅡ) and signal transduction molecules 7(Smad7) in rats myocardium and the intervention effects of Didang Tang and its split recipes. Method: The 12 healthy male SD rats were chosen randomly as normal group, and other 105 SD male rats were injected intraperitoneally with STZ to induce diabetes(DM) rat models, which were randomized into model group, Didang Tang group, leech and mang worm group, peach kernel and rheum officinale group, and valsartan group, receiving corresponding intervention. At the end of 8-week treatment, fasting blood glucose(FBG) was detected by full-automatic biochemical analyzer,pathomorphological change of myocardium was observed through hematoxylin-eosin staining,and the protein expression of TGF-β1, TGF-β RⅡ and Smad7 were assessed by Western blot. Result: Compared with the normal group,cell hypertrophy was observed in myocardial tissues, with obvious infiltration of inflammatory cells, significant increase in TGF-β1, TGF-β RⅡexpression and significant decrease in Smad7 expression(P<0.01). Compared with the model group, Didang Tang could significantly down-regulate TGF-β1 and TGF-β RⅡexpression and significantly down-regulate Smad7 expression(P<0.05, P<0.01). Compared with the diabetic rat models, the split recipe groups could down-regulate TGF-β1 expression and improve myocardial damages, but the effect was inferior to that of whole prescription group. Conclusion: Didang Tang could relieve cardiac fibrosis of diabetic rats and its mechanism may be associated with down-regulating TGF-β1 and TGF-β RⅡexpression in myocardium of diabetic rats and up-regulating Smad7 expression. In addition, the prophylactic and therapeutic effect of Didang Tang was better than that of its split recipes.The treatment of 'expelling heat, removing blood stasis and dredging collaterals' was associated with inhibiting TGF-β1/Smad7 signal transduction pathway.

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储全根,刘新萍,张凯,毕华剑,吴元洁,周雪梅,刘德胜,董妍妍.抵当汤及其拆方对糖尿病大鼠心肌TGF-β1,TGF-β RⅡ及Smad7蛋白表达的影响[J].中国实验方剂学杂志,2016,22(1):93~97

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  • 收稿日期:2015-02-13
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  • 在线发布日期: 2015-12-29
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