结核分枝杆菌感染巨噬细胞后NF-κB信号通路与凋亡和自噬的调控机制研究

项目名称： 结核分枝杆菌感染巨噬细胞后NF-κB信号通路与凋亡和自噬的调控机制研究

项目编号： No.81460246

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王仙

作者单位： 石河子大学

项目金额： 51万元

中文摘要： 结核病是由结核分枝杆菌（Mycobacterium tuberculosis，MTB）感染引起的传染性疾病，目前MTB的致病机制尚不明确，主要与宿主的免疫功能和MTB毒力有关。巨噬细胞是抵抗MTB感染和扩散的主要效应细胞。我们前期研究结果显示巨噬细胞吞噬MTB后NF-κB信号通路被激活，暗示NF-κB信号通路可能参与巨噬细胞与MTB之间的免疫平衡调节；雷公藤甲素可通过调节NF-κB信号通路对机体免疫平衡进行调控。本课题将主要研究以下问题：（1）不同毒力和当地耐药MTB感染巨噬细胞后对NF-κB信号通路的调节机制；（2）用NF-κB信号通路抑制剂和雷公藤甲素对巨噬细胞内NF-κB信号通路进行调节，观察MTB感染后巨噬细胞的凋亡及自噬现象，并研究其发生机制；（3）利用小鼠模型研究NF-κB信号通路在机体巨噬细胞与MTB免疫平衡中的功能；（4）雷公藤甲素对不同毒力和当地耐药MTB感染的防治研究。

中文关键词： 结核分枝杆菌；巨噬细胞；信号通路；细胞凋亡

英文摘要： TTuberculosis caused by the pulmonary pathogen mycobacterium tuberculosis (MTB) is a world wide infectious disease, the precise nature of the pathogenic mechanism of MTB has not been completely defined, primarily relate to the balance of protective immune function and bacterial virulence. Macrophages is the main effector cell response to MTB infection. Our preliminary results showed that NF-κB is activated in macrophages when response to MTB, indicated that NF-κB pathway may participate the immunologic balance regulation between macrophages and MTB; In addition, triptolide is involved in immunologic regulation through inhibiting NF-κB activation. This study is to analyze the followings: (1) NF-κB pathway activation mechanism in macrophages when response to different virulence and local drug resistant MTB; (2) The effect and mechanism of NF-κB pathway on macrophage apoptosis and autophagy through the inhibitor of NF-κB pathway and triptolide; (3) The function of NF-κB pathway in the balance of host immune system and MTB by mouse tuberculosis model; (4) The therapeutic effect of triptolide on different virulence and local drug resistant MTB.

英文关键词： mycobacterium tuberculosis;macrophage;signaling pathway;apoptosis