线粒体电压依赖性阴离子通道蛋白调节足细胞炎症小体激活在糖尿病肾病中的致病机制

项目名称： 线粒体电压依赖性阴离子通道蛋白调节足细胞炎症小体激活在糖尿病肾病中的致病机制

项目编号： No.81470954

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： 娄探奇

作者单位： 中山大学

项目金额： 73万元

中文摘要： 肾脏炎症状态与糖尿病肾病（DN）的进展密切相关，而炎症小体是炎症反应的核心。在前期研究中，我们发现高糖可以引起足细胞炎症小体表达增加，而且炎症小体的表达与足细胞凋亡和线粒体功能受损呈正相关。有研究提示，线粒体依赖性阴离子通道蛋白(VDAC)可能是其中重要的调节因子，但机制尚不清楚。本研究假设：糖尿病肾病时升高的血糖可通过调节VDAC的表达，引起足细胞诱导型一氧化氮合酶（iNOS）表达的改变，从而影响线粒体活性氧（ROS）的产生，进而激活炎症小体，导致足细胞损伤和凋亡增加，加速糖尿病肾病的进展。本研究拟通过细胞和动物实验，探讨炎症小体在足细胞线粒体功能障碍中的作用，明确糖尿病肾病足细胞VDAC-iNOS-ROS通路对炎症小体激活的重要意义，为DN的防治提供新的靶点。

中文关键词： 电压依赖性阴离子通道蛋白；炎症小体；糖尿病肾病；足细胞

英文摘要： The inflammatory state of kidney is intimately related with the progression of diabetic nephropathy (DN) while the inflammasomes act as the core of inflammation reaction. In our previous study, we found that high glucose could increase the expression of inflammasomes in podocytes which is positively correlated with the podocyte apoptosis and dysfunction of mitochondria.VDAC has been reported to be an important regulatory factor while the mechanism is still unclear.Therefore, we assume that: in diabetic nephropathy, VADC expression may be adjusted by the metabolic factors(including high glucose),which affects the production of ROS through altering the expression of iNOS,thus contributing to the activation of inflammasomes, eventually causing podocytes injury and increased apoptosis and the acceleration of diabetic nephropathy.This study intends to investigate the effects of inflammasomes in podocytes injury through cells and animal experiments and the role of VDAC-iNOS-ROS in the regulation of inflammasomes activation in podocyte in diabetic nephropathy. The study is expected to reveal the new prevention and therapeutic target in diabetic nephropathy.

英文关键词： VDAC;inflammasomes;diabetic nephropathy;podocyte