芪丹地黄颗粒对糖尿病肾病足细胞EMT的调控机制研究

Diabetic kidney disease (DKD) has become a serious public health problem. Proteinuria is not only the DKD marker, but also the important factor that aggravates DKD.Studies have shown that the decrease in the number and density of the podocyte is closely related to the occurrence of proteinuria and the degree of DKD. Previous studies have shown that QDDHG can effectively reduce the DKD proteinuria at the same time, improving the structure of the kidney, inhibition of podocyte beta catenin, FSp1 related gene expression, improve E - carntine gene expression. We hypothesized that QDDHG may regulate the epithelial-mesenchymal transformation (EMT) of the podocyte through the Wnt/ beta-catenin pathway, protect the podocyte, reduce the proteinuria, and delay the development of DKD. Therefore, this project intends to use db/db mouse to observe the expression of characteristic protein and EMT marker protein in mouse podocyte. Wnt pathway specific inhibitors and agonists were used to intervene in the podocyte under high glucose conditions, and the regulation mechanism of the Wnt pathway on the podocyte EMT of DKD was illuminated in combination with the internal experiments. On this basis, the intervention effect of QDDHG on the Wnt/β-catenin pathway of DKD and its regulated podocyte EMT was eluciated by using the pharmacological methods of drug administration and serum pharmacology.It is important to elucidate the prevention and treatment mechanism of DKD and proteinuria in Traditional Chinese medicine.

糖尿病肾病（DKD）已是严重公共卫生问题。蛋白尿不仅是DKD标志，也是DKD加重的重要因素。研究表明足细胞数量和密度的减少与蛋白尿发生及疾病程度密切相关。芪丹地黄颗粒（QDDHG）可有效减少DKD蛋白尿，改善肾组织结构，抑制足细胞β-catenin、FSp1相关基因表达，提高E-carntine基因表达。我们推测，QDDHG可能通过调控Wnt/β-catenin通路抑制足细胞上皮-间充质转化（EMT），保护足细胞，降低蛋白尿。因此，本项目拟利用db/db小鼠，观察小鼠肾脏足细胞特征性蛋白、EMT标志蛋白表达；应用Wnt通路特异性抑制剂和激动剂干预高糖条件下足细胞，结合体内实验明确Wnt通路对DKD足细胞EMT的调控机制。在此基础上，采用体内给药及血清药理学方法，阐明QDDHG对糖尿病肾病Wnt/β-catenin通路及其调控的足细胞EMT的干预效应。这对于减少DKD蛋白尿具有重要意义。

糖尿病肾病（DKD）发病人数多，危害重。蛋白尿不仅是DKD标志，也是DKD加重的重要因素。前期的研究表明足细胞数量的减少与蛋白尿发生及疾病程度密切相关。本项目以足EMT的调控机制为切入点，围绕Wnt/β-catenin信号通路，对芪丹地黄颗粒防治糖尿病肾病的作用机理开展研究。研究显示芪丹地黄颗粒（QDDHG）可有效减少糖尿病肾病小鼠的蛋白尿，改善肾组织病理结构，抑制肾小球wnt4、β-catenin相关蛋白的表达，提高E-cadherin、ZO-1蛋白表达水平。QDDHG主要是通过调控Wnt/β-catenin通路wnt4、β-catenin蛋白的表达，抑制足细胞EMT，从而保护足细胞，降低蛋白尿。本项目的研究为芪丹地黄颗粒在临床推广应用提供科学依据，为糖尿病肾病的治疗提供候选药物。