蛋白酶活化受体2在糖尿病肾病间质炎症中的作用及机制研究

项目名称： 蛋白酶活化受体2在糖尿病肾病间质炎症中的作用及机制研究

项目编号： No.81200532

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 任韫卓

作者单位： 河北医科大学

项目金额： 25万元

中文摘要： 肾间质炎症反应过程是糖尿病肾病的重要病理生理基础。蛋白酶活化受体2（PAR2）和炎症、糖尿病、肾脏病变有着密切的联系，但PAR2在糖尿病肾病炎症中的作用未见报道。我们的前期研究发现PAR2在高糖环境下表达明显升高，炎症标志物表达升高，提示其在糖尿病肾病中可能起促炎作用。为此，本项目围绕高糖负荷下PAR2和炎症及后续纤维化之间的关系及机制进行深入研究。首先研究高糖负荷时肾小管上皮细胞PAR2的变化及对炎症的影响，明确PAR2在糖尿病肾脏炎症中的确切作用；然后基于微点阵技术提示PAR2活化和Sirt1之间有一定关系、Sirt1在炎症、肾脏疾病中丰富的作用，且尚未有关Sirt1在糖尿病肾病炎症中的报道，本项目将探究Sirt1在糖尿病肾病炎症中的作用，并明确它与PAR2之间的关系，即PAR2在糖尿病肾脏炎症中发挥作用是否呈Sirt1依赖性。旨在揭示糖尿病肾病发病新机制，为从抗炎角度治疗找到新靶向。

中文关键词： 蛋白酶活化受体2；Sirt1；糖尿病肾病；炎症；纤维化

英文摘要： Renal interstitial inflammation is the important pathophysiologic foundation of diabetic nephropathy. Protease-activated receptors 2(PAR2) correlates tightly with inflammation ,diabetes and renal disease. However, the role of PAR2 in diabetic renal inflammation is unknown. So,we made a research and first time found that the expression of PAR2 protein increased significantly under high glucose(HG) condition. At the same time, the increased interleukin-1β(IL-1β) level was detected. These data suggest a pathogenic role of PAR2 in inflammation of diabetic nephropathy. Based on above, we will reasearch the subject deeply to explore the proinflammatory effect of PAR2 in diabetic nephropathy and its mechanism. First, we will investigate the expression of PAR2 and the inflammation markers such as IL-1β, monocyte chemoattratctant protein-1(MCP-1) under HG condition in vivo and in vitro. And we will observe the effect of PAR2 silencing , PAR2 overexpression and nature/synthetic PAR2 agonist on the inflammation markers. So, it is aimed to clarify the potential proinflammatory role of PAR2 in the progression of diabetic nephropathy. Next, a report recently indicates the relationship between PAR2 and the silent information regulator genes(sirtunes, Sirt) in Human Embryonic Kidney cells (HEK293) via cDNA microarray analys

英文关键词： proteinase-activated receptor2；Sirt1；diabetes mellitus；inflammation；fibrosis