基于TGF-β/smads/ILK/GSK-3细胞信号通路探讨芪归益肾方延缓肾脏纤维化进展机制的实验研究

项目名称： 基于TGF-β/smads/ILK/GSK-3细胞信号通路探讨芪归益肾方延缓肾脏纤维化进展机制的实验研究

项目编号： No.81473633

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 魏明刚

作者单位： 苏州大学

项目金额： 76万元

中文摘要： 已有工作证实以健脾益肾，活血通络为原则创立的中药方剂芪归益肾方对减少尿蛋白漏出、减轻细胞外基质聚集和保护足细胞方面的作用确切。本研究是在以往研究基础上的进一步深入。基于纤维化改变在慢性肾脏病病变进展中的重要作用，结合本课题组的研究基础和相关文献提出细胞信号转导通路在肾脏纤维化调控方面的核心地位。拟以调控细胞信号转导，延缓肾脏纤维化进展的视角，探讨芪归益肾方延缓肾脏纤维化的机制及有效性。应用具有自主知识产权的方剂芪归益肾方，以模拟人类病变情况的动物模型为基础，结合肾小管上皮细胞不同培养条件下的细胞学实验，观察调控TGF-β/smads/ILK细胞信号通路对细胞因子、细胞周期基因、肾小管间质转分化、核因子和细胞外基质及其代谢酶表达的作用。研究采用蛋白免疫印记、荧光示踪和基因芯片等技术手段验证中医药在延缓肾脏纤维化方面的机制及有效性。

中文关键词： 中医药治疗；肾脏纤维化；细胞信号通路；实验研究

英文摘要： We have confirmed that the Chinese herbs of decoction qigui yishen can reduce urinary leakage of protein, decrease the aggregation of extracellular matrix (ECM) and lseeen the damage of podocyte. The prescription was set up by the principle of traditional Chinese medicine, which means that invigorating the spleen and kidney, promoting blood circulation to remove meridian obstruction. This research is in-depth study basing on the previous research. It is well known to all, fibrosis change has important pathology role to chronic kidney disease(CKD). Basing on the previous study of us and related literatures in recently years, we put forward the point of view that cell signal transduction pathways has the core action to the renal fibrosis. We want to use the idea 'regulation of cell signal transduction, delay the renal fibrosis progress' as the starting point to explore that why 'decoction qiguiyishen' can delays the renal fibrosis. Application with independent intellectual property rights of prescription, we will confirmed our ides and the efficiency of 'decoction qigui yishen' by the experiment In vivo and in vitro. The study of in vitro will base on the animal models, which has the similar lessions of CKD as the human disease. As to the experiments in vivo, we will use the mutil-level method to observe the cultivation of the renal tubular epithelial cells and the action of chinese herbs to it. We will observe that through regulating the cell signaling pathways of 'TGF-beta/smads /ILK/GSK-3' , the Chinese herbs maybe change the expression of cytokines, relieve the renal tubular interstitial transdifferentiation and nuclear factor, reduce the accumulation of ECM and affect the expression of the metabolic enzyme of ECM. In order to verify the efficacy and mechanism of traditional Chinese medicine is usefulto delay the course of renal fibrosis, we will use many advanced technology such as immune protein imprinting, fluorescent tracer technology and gene array,and so on.

英文关键词： treatment of traditional chinese medicine;renal fibrosis;cell signaling pathway;experimental research