基于蛋白质组学研究黄连效应物质群治疗2型糖尿病的多靶点作用机制

项目名称： 基于蛋白质组学研究黄连效应物质群治疗2型糖尿病的多靶点作用机制

项目编号： No.81473448

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： 徐丽君

作者单位： 华中科技大学

项目金额： 75万元

中文摘要： 黄连用于治疗消渴症已有2000余年历史。现代研究表明，其主要成分小檗碱、黄连碱、阿魏酸等均具有一定的降糖调脂作用，且其作用靶点、环节各异，与 DeFronzo教授提出的联合使用多种药物以纠正多重病理生理缺陷的T2DM用药原则相吻合。基于课题组前期研究成果：黄连粉末给药治疗T2DM效果佳、起效快、作用稳定，优于等同剂量的小檗碱和黄连煎剂，提出构建黄连'特定'效应物质群以治疗多重病理生理缺陷之T2DM的设想，本课题采用超临界萃取方法、科学运用超临界介质提取黄连效应物质群；比较提取物对糖尿病小鼠/大鼠模型的疗效以筛选确定超临界萃取条件；借助HPLC/LC-MS、NMR等方法建立效应成分群指纹图谱、测试其组成比例、研究其结构特征；运用蛋白质组学和生物信息学技术，从终端研究该效应物质群治疗T2DM的多靶点作用机制，探讨'特定'效应物质群降糖调脂的作用特点，为将其开发成中药1.2类新药奠定基础。

中文关键词： 黄连；2型糖尿病；效应物质；蛋白质组学

英文摘要： Coptis chinensis has a long history to treat diabetes for 2000 years. As the main components of Coptis chinensis, berberine, coptisine and ferulic acid have been proved to possess anti-hyperglycemia and anti-dyslipidemia properties. The mechanisms underlying this efficacy are related to different action targets and signaling pathways. We previously found that Coptis powder was superior to the berberine and Coptis decoction with the corresponding dose respectively in the treatment of type 2 diabetes (T2DM). However, the mechanism remains unclear. Since multiple pathophysiological dysfunctions are involved in the development of T2DM,we try to test our hypothesis that the special materials consisted of effective substances in Coptis chinensis act synergistically via multiple targets in the treatment of T2DM. Experiments have been designed to extract the effective materials by the way of supercritical fluid extraction(SFE) as well as to select and identify the technical conditions on SFE by comparing the effects on diabetic mice/rats model. Meanwhile,the fingerprint of the effective materials will be established and the composition and structural characteristics of effective materials will be tested by HPLC/LC-MS and NMR assays. To explore the mechanisms underlying the anti-diabetic efficacy of these effective materials on multiple targets, we will apply proteomics and bioinformatics techniques. The successful completion of the proposed research will illustrate the anti-diabetic mechanisms of the effective materials contained in Coptis chinensis on multiple targets, based on which we will try to develop a 1.2 class new drug of traditional Chinese medicine.

英文关键词： Rhizoma Coptidis;type 2 diabetes;effectors;proteomics