糖通饮通过干预microRNA-21调控TGF-β1/Smad信号通路防治糖尿病肾病分子机制研究

DN是引起终末期肾衰的主要原因，迄今该病发病机制仍未完全明确且治疗困难，对其发病机制和有效药物的探究一直是糖尿病慢性并发症防治的研究重点。前期研究发现，以益气养阴保肾、活血化痰泄浊立法的糖通饮临床疗效显著，且能抑制DN大鼠肾组织TGF-β1/Smad2、3信号通路的激活；近年文献报道，miRNA-21参与了TGF-β1通路的调控，促进DN肾小球系膜细胞增殖并继发纤维化，成为DN的潜在治疗靶点。基于课题组前期实验结果及文献研究，提出糖通饮通过干预miRNA-21的表达来调控TGF-β1/Smad信号通路，从而发挥防治糖尿病肾病作用的假说。项目以整体动物与细胞模型为研究对象，用糖通饮进行干预，围绕microRNA-21对TGF-β1/Smad信号通路的调控，阐明糖通饮保护肾组织，防治DN的分子机制，为糖通饮的推广和开发提供科学依据，丰富该方的临床运用理论，促进中医药对慢性复杂性疾病的治疗应用。

Diabetic nephropathy is the main cause of end-stage renal failure.Up to now, the pathogenesis of DN has not been fully identified and it is difficult to treat it.The exploration of the pathogenesis of DN and effective drugs has always been the focus of research on the prevention and treatment of chronic complications of diabetes.National famous Chinese medicine expert professor LingXiangli with Invigorating qi and nourishing kidney,promoting blood circulation,resolving phlegm and relieving turbidity initiatives experience of Tangtongyin.premenstrual study found that the clinical curative effect is distinct, while reducing proteinuria with the advantages of improve glucolipid metabolic disorders, can inhibit the activation of kidney TGF-β1/Smad2,3 signaling pathways of DN model rat;In recent years,it has been reported that microRNA-21 can promote the proliferation of DN mesenchymal cells and secondary fibrosis,and microRNA-21 is involved in the regulation of TGF-β1 pathway, becoming a potential therapeutic target for DN.Based on the preliminary experimental results of the research group and literature studies,we proposed the hypothesis that Tangtongyin can regulate TGF-β1/Smad signaling pathway by interfering the expression of microRNA-21, so as to play a role in the prevention and treatment of diabetic nephropathy. This project take the whole animal and cell models as the research object, using Tangtongyin to intervene, around the regulation of TGF-β1/ Smad signaling pathway by microRNA-21,clarify that Tangtongyin can protect kidney tissues,the molecular mechanism of prevention and treatment of DN, provide scientific basis for the promotion and development of Tangtongyin, enrich and perfect the clinical application theory of this prescription, promote the application of traditional Chinese medicine in the treatment of chronic complexity diseases.