NOD2介导的自噬在糖尿病肾病肾小管损伤中的作用及机制研究

项目名称： NOD2介导的自噬在糖尿病肾病肾小管损伤中的作用及机制研究

项目编号： No.81500557

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 都鹏超

作者单位： 滨州医学院

项目金额： 18万元

中文摘要： 糖尿病肾病肾小管损伤发病机制的研究目前集中在炎症介导的免疫平衡，其中固有免疫应答的作用日益凸显。核苷酸结合寡聚化结构域2（NOD2）是位于胞浆内的模式识别受体，在多种自身免疫性疾病中发挥重要作用，但其在糖尿病肾病肾小管损伤中的作用机制尚不清楚。前期工作证实NOD2在糖尿病肾病患者及糖尿病小鼠的肾皮质中表达显著升高，且在浸润的炎症细胞中高表达；高糖刺激的肾小管上皮细胞中NOD2表达明显升高，且呈浓度依赖性；同时基因敲除小鼠实验表明NOD2基因缺失明显改善糖尿病肾病肾小管自噬功能，提示NOD2参与糖尿病肾病肾小管自噬损伤。本项目将以NOD2为中心，围绕肾小管上皮细胞自噬改变，采用细胞生物学、基因敲除小鼠等技术深入探讨NOD2-自噬在糖尿病肾病肾小管损伤中的分子生物学机制，阐明NOD2在肾脏实质细胞免疫平衡及细胞稳态中的重要作用，以期从减轻炎症反应、恢复自噬功能角度，找到糖尿病肾病治疗的新思路。

中文关键词： 糖尿病肾病；肾小管损伤；炎症反应；细胞自噬

英文摘要： The pathogenesis of the tubular injury in diabetic nephropathy (DN) is currently focused on the balance of inflammation-mediated immunity, and the role of the innate immune response has been increasingly prominent. Nucleootide-binding oligomerization domain containing 2 (NOD2), a member of cytosolic pattern recognition receptors, plays an important role in a variety of autoimmune diseases, but the role in the the mechanism of the tubular injury in DN is still unclear. Previous work demonstrated that the expression of NOD2 was significantly increased in the renal cortex from DN patients and diabetic mice, and closely related to the infiltrated inflammatory cells; Also, it was found that the NOD2 expression was significantly increased in the renal tubular epithelial cells with high glucose treatment in a concentration-dependent manner; Meanwhile the results of knockout-mice experiments showed that the deficiency of NOD2 could significantly improve the state of autophagy in renal tubular cells, suggesting that NOD2 might be involved in the autophagy injury in diabetic renal tubules. Therefore, this project aims to explore the mechanism of NOD2-mediated autophagy in the renal tubular epithelial cells and to clearify the role of NOD2 in the immunity balance and cellular homeostasis in the kidney parenchyma cells, by using cell biologic, gene knockout mice and other molecular biologic techniques. So，to relieve the inflammation and restore the autophagic function will be a new way to cure DN.

英文关键词： diabetic nephropathy;tubular injury;inflammation;autophagy