小檗碱对糖尿病肾病中G蛋白偶联受体激酶调控系膜细胞G蛋白偶联信号的作用

项目名称： 小檗碱对糖尿病肾病中G蛋白偶联受体激酶调控系膜细胞G蛋白偶联信号的作用

项目编号： No.81073109

项目类型： 面上项目

立项/批准年度： 2011

项目学科： 生物科学

项目作者： 唐丽琴

作者单位： 安徽医科大学

项目金额： 10万元

中文摘要： 糖尿病属中医"消渴"范畴，小檗碱是黄连的主要有效成分，是其治疗消渴的物质基础。糖尿病肾病（DN）是糖尿病常见且严重的并发症，成为糖尿病的主要死亡原因之一，信号转导通路的异常改变是DN形成的重要机制和研究热点。Ｇ蛋白偶联受体激酶 (GRKs)是调控Ｇ蛋白偶联受体（GPCRs）介导的信号转导通路的重要物质，GRKs表达的变化可能会影响到肾小球系膜细胞的生理和病理功能。本研究运用Western Blot等分子生物学技术和方法，在本课题组前期对DN大鼠肾小球系膜细胞信号通路研究的基础上，首次探讨GRKs在DN大鼠肾小球系膜细胞中的亚型表达以及小檗碱对其的影响，进一步阐明DN的发病机制及深入认识小檗碱治疗DN的分子机制，为临床合理应用小檗碱治疗DN提供更加充分的理论依据,并试图寻找新的药物作用靶点，为开发新型治疗DN药物奠定基础。

中文关键词： 小檗碱；糖尿病肾病；系膜细胞；Ｇ蛋白偶联受体激酶；Ｇ蛋白

英文摘要： Diabetes mellitus(DM) belongs to the type of "wasting-thirst" in traditional chinese medicine. Berberine, one of the main ingredients of Rhizoma Coptidis, has essential effect on treating DM. Diabetic nephropathy(DN), one of the major and serious microvascular complictions of DM, has become the main cause of end-stage renal disease worldwide. Abnormal change of signal transduction path has contributed to mechanism of DN, which has been hot focus of this research. G protein-coupled receptor kinase(GRKs) have been important substances regulating signal transduction path of G-protein-coupled receptors. Diversity of GRKs expression maybe has an effect on physiological and pathological functions of mesangial cells. In our preceding experiments, we have already researched the signal transduction path of mesangial cells in the mouse model of DN with technologies and methods of molecular biology such as western blot. It is the first time that we approach how GRKs' isoforms express and berberine has an impact on a series of the process. And furtherly we clarificate the mechanism of DN and realize that berberine has the role in it. It provides new evidence that berberine has been utilized in clinical application reasonably and that we try to explore new available targets affected by other new drugs.

英文关键词： Berberine; diabetic nephropathy; mesangial cells; G protein-coupled receptor kinases; G protein