Th17/IL-17信号轴对原发性肾病足细胞损伤的分子免疫机制研究

The primary nephrotic syndrome (PNS) is one of the most important cause of children with chronic renal failure, and bring great physical and psychological burden to patients and their families. T cell dysfunction of Th1 / Th2 imbalance theory can not interpret the pathogenesis of PNS. Our previous studies found that Th17 cells increased in children with PNS, Treg cells reduced in children with PNS , and for the first time found a significant increase in cytokine IL-17 mRNA expression and protein expression in serum and renal tissue compared with normal control, Th17/Treg cell ratio imbalanced and Th17/IL-17 axis amplification effect is an important mechanism leading to podocyte injury , resulting in a large number of proteinuria . Therefore, this project intends to adopt podocyte cell in vitro experiments , rats with adriamycin nephrosis in vivo experiments to clarify the pathogenesis of PNS from a new perspective of Th17/IL-17- podocyte injury - proteinuria way ; RNAi technology was used to block the IL-17 gene expression , to prevent PNS podocytes intervention and prevent early glomerular sclerosis lesions .

原发性肾病综合征（PNS）是引起我国儿童慢性肾功能衰竭的重要原发疾病，给患儿及家庭、社会带来极大的身心及经济负担。既往的T细胞功能紊乱即Th1/Th2失衡理论不能诠释PNS的发病机理。本课题组前期研究发现PNS患儿外周血单个核细胞中Th17细胞比例增高、Treg细胞比例降低、并且首次发现患儿血清及肾组织中IL-17因子mRNA表达和蛋白表达较正常对照显著增加，推测Th17/Treg细胞比例失衡、Th17/IL-17轴效应异常放大是导致肾小球足细胞损伤、产生大量蛋白尿的重要机制。因此本项目拟采用鼠肾脏足细胞株进行体外实验、阿霉素肾病大鼠进行体内实验，从Th17/IL-17-足细胞损伤-蛋白尿途径，以新的视角阐明儿童PNS的部分发病机制；以RNAi 基因沉默技术阻断IL-17基因表达，干预PNS的足细胞病变为防止早期肾小球硬化、改善预后寻找新的治疗途径。

原发性肾病综合征（PNS）是引起我国儿童慢性肾功能衰竭的重要原发疾病，给患者及家庭、社会带来极大的身心及经济负担。既往的T细胞功能紊乱即Th1/Th2细胞失衡不能诠释PNS的发病机理。本项目从Th17/IL-17-足细胞损伤-蛋白尿途径，采用阿霉素肾病大鼠进行体内实验，以RNAi基因沉默技术阻断IL-17基因表达，干预PNS的足细胞病变为防止早期肾小球硬化、改善预后寻找新的治疗途径。研究结果显示，Th17/IL-17异常活化参与足细胞损伤、继而引起肾小球滤过屏障结构破损，导致大量蛋白尿的产生，RNAi技术沉默IL-17基因后对阿霉素肾病大鼠的有效干预，可望为临床原发性肾病综合征足细胞损伤的认识展示一个新的视野，为今后临床合理干预、寻找治疗靶标提供理论基础。