Mcl-1在结核分枝杆菌感染宿主巨噬细胞中凋亡的调控作用及其机制的研究

结核分枝杆菌是典型的胞内致病菌，可导致其宿主细胞不能正常凋亡，若能使吞噬有结核杆菌的宿主巨噬细胞启动凋亡程序正常凋亡，则可消灭感染的结核杆菌，避免结核在体内潜伏或者播散。髓样细胞白血病-1(Mcl-1)基因的主要作用是抑制细胞凋亡，是决定细胞生存的关键因素。本研究通过细胞体外和动物体内实验，分别用靶向Mcl-1的shRNA沉默Mcl-1宿主基因、用信号通路阻断剂阻断Mcl-1表达，观察不同毒力的结核杆菌感染宿主后，能否通过增加感染巨噬细胞的凋亡达到杀灭结核杆菌的目的，并研究其发生机制，为治疗和预防结核病提供新方法和思路。

Mycobacterium tuberculosis survive and replicate in the host macrophage is critical to its pathogenesis. There is evidence that apoptosis can't occur in vivo during the course of affected macrophage by mycobacterium tuberculosis. Apoptosis was shown to reduce mycobacterium tuberculosis disseminated in vitro. So, if the affected macrophage can apoptosis, mycobacterium tuberculosis can be controlled. Myeloide cell leukemia-1(Mcl-1) is a member of bcl-2 family. The main function of Mcl-1 is to promoted cell survival and protected cell apoptosis. To study the role of Mcl-1 in mycobacterium tuberculosis infected macrophages, we use short hairpinRNA(shRNA) targeting Mcl-1 gene and signal pathway inhibitor knock down Mcl-1 gene in vitro or in vivo. It can demonstrate further the mechanism that if different virulent mycobacterium tuberculosis strains infected macrophage cause more apoptosis to kill mycobacterium tuberculosis. Mcl-1 is a promising target for antisense therapy of tuberculosis.