虫草多糖活性片段的筛选及分子作用机制的研究

项目名称： 虫草多糖活性片段的筛选及分子作用机制的研究

项目编号： No.81202900

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 王莹

作者单位： 中国药科大学

项目金额： 24万元

中文摘要： 申请人首次发现来自虫草菌丝体的虫草多糖治疗慢性肾功能衰竭，是通过抑制TGF-β1而发挥效应的。为探明虫草多糖中最基本的活性片段，拟采用化学、生物等手段降解获取虫草多糖若干片段，在TGF-β1诱导的细胞模型中进行筛选，寻找最佳活性片段。进而从分子水平多维动态地揭示虫草多糖活性片段在TGF-β1诱导的上皮-间质转化过程中，对以SMAD家族蛋白为代表的关键因子的影响，寻找虫草多糖活性片段在细胞内的信号通路及其作用靶点。最终运用TGFβRⅡ基因敲除小鼠模型进行体内靶点验证。受多糖具有双向免疫效应启发，假说虫草多糖活性片段对TGF-β1表达水平有双向调控效应，在HK-2细胞模型下，与小分子TGF-β1抑制剂比较，揭示两者作用机制的本质差异。通过本课题对虫草多糖活性片段的研究，初步揭示多糖特有的双向作用机制，对冬虫夏草治疗慢性肾病药效物质基础研究有所突破，为中药现代化的发展作出贡献。

中文关键词： 虫草多糖活性片段；PDGF-BB；活性氧；炎症；NADPH氧化酶

英文摘要： It was the first time we found one polysaccharide from Cordyceps Sinensis mycelium. It can treat chronic renal failure through TGF-β1 pathway. We'll get the basic active fragments from Cordyceps Sinensis polysaccharide (CPS) by chemical or biological methods, then find the best fragment through TGF-β1 induced cell model. The influence of CPS active fragments to the key factors in TGF-β1 induced epithelial-mesenchymal transition, such as SMAD family, will be revealed dynamically on the molecular level. The celluar signal pathway and the target of CPS active fragments will be found. TGF-β receptor Ⅱ knockout mice will be used to validate the effect in vivo. As most of the polysaccharides have the bi-directional immunomodulatory activities, CPS active fragments will be supposed to have bi-directional regulation on TGF-β1 protein. We'll use HK-2 cells to reveal the mechanism differences between CPS active fragments and other micromolecular TGF-β1 inhibitors. In a word, this project will be focused on the research of CPS active fragments to reveal the special bi-directional regulation. The project will break through the used research on the chronic renal failure therapeutical effect of Cordyceps and make some contribution to the moderniaztion of traditional Chinese medicine.

英文关键词： Cordyceps sinensis polysaccharide fragment；PDGF-BB；Reactive oxygen species；Inflammation；NADPH oxidase