MicroRNA-124协同TGF-β1-Smad4调节小胶质细胞内毒素耐受的机制

项目名称： MicroRNA-124协同TGF-β1-Smad4调节小胶质细胞内毒素耐受的机制

项目编号： No.81201252

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 秦永伟

作者单位： 南通大学

项目金额： 23万元

中文摘要： 败血症或全身炎症反应综合症（SIRS）致外周多器官感染和衰竭的机制研究有较大进展，但对于其导致中枢神经系统（CNS）炎症或感染机制的研究甚少。本课题首先建立败血症致CNS感染的模型，明确参与内毒素耐受的关键分子Smad4在CNS内炎症反应过程中的表达变化；接着分析CNS的小胶质细胞内毒素耐受下，Smad4的转录调节机制，以及在内毒素耐受条件下，参与调节小胶质细胞极性状态的重要分子miR-124的变化；最后分析miR-124协同TGF-β1-Smad4通路调节小胶质细胞活化及免疫耐受的机制，以及这种机制与败血症致CNS炎症性疾病病程之间的相互关系。通过本实验试图寻找能够控制小胶质细胞保持静息或活化状态的关键靶分子，为CNS炎症或免疫性疾病的发病机制及治疗提供新的研究思路。

中文关键词： 小胶质细胞；内毒素耐受；microRNA；极化；

英文摘要： The mechanisms of peripheral multi-organ infection and failure caused by sepsis or systemic inflammatory response syndrome (SIRS) have been making great progress, but little research about causing central nervous system (CNS) inflammation or infection had been made. In this project, we will establish a model of sepsis caused by CNS infection firstly, meanwhile, clarify the expression of key molecule-Smad4 involving in endotoxin tolerance during the CNS inflammation process; followed by analysis the mechanism of transcriptional regulation for Smad4 in microglia under the condition of endotoxin tolerance in CNS, detect the expression of an important molecule-miR-124, which involve in the regulation of polarity state of microglia; analysis the mechanism of miR-124 cooperate with TGF-β1-Smad4 pathway which regulates the activation of microglia cells and immune tolerance, as well as the interrelationship between this mechanism with CNS inflammatory disease progression caused by sepsis. This project is trying to find some key target molecules which can control resting or activated state of microglia, providing new insight into clarifying the mechanism of pathogenesis and treatment of inflammation or autoimmune disease in CNS.

英文关键词： microglia；endotoxin tolerance；microRNA；polarization；