结核分枝杆菌诱导宿主巨噬细胞凋亡机制初探  

The mechanism of macrophage apoptosis induced by Mycobacterium tuberculosis

作　　者：夏飞[1] 刘胜武[1] 魏雅稚[1] 肖凌[1] 

机构地区：[1]武汉大学医学院免疫学系,430071

出　　处：《中华微生物学和免疫学杂志》2005年第6期463-468,共6页Chinese Journal of Microbiology and Immunology

摘　　要：目的探讨结核杆菌感染中巨噬细胞凋亡的信号传导通路及分子机理。方法用透射电镜、荧光染色对凋亡细胞的形态特征进行分析;琼脂糖凝胶电泳检测巨噬细胞DNA片段化水平;流式细胞术测定不同时期小鼠巨噬细胞凋亡率、膜表面Toll样受体2(TLR2)和胞内Bcl2蛋白的水平。结果结核杆菌强毒力株H37Rv感染组的巨噬细胞凋亡率在1～7d内逐渐升高,至7d时最高可达32.2%,感染的9～11d以后,凋亡率逐渐降低;H37Rv感染组Bcl2水平于感染9～11d后逐渐升高,与卡介苗(BCG)组比较差异有统计学意义;H37Rv感染组和BCG组的巨噬细胞膜表面的TLR2水平均高于正常对照组;各组组内不同时期的TLR2水平无明显变化。结论结核杆菌H37Rv株在感染的早期对宿主巨噬细胞有较强的致凋亡作用,而Bcl2表达的增加能显著抑制这种凋亡。结核杆菌在体内感染过程中,TLR2蛋白可能与巨噬细胞凋亡及Bcl2表达无关。Objective To study the signal transduction pathway of Mycobacterium tuberculosis (Mtb)-induced apoptosis of alveolar macrophages(AMΦ). Methods Morphological change of macrophages was observed with transmission electron microscopy and fluorescence staining. Agarose gel electrophoresis was used for the qualitatively detection . The apoptosis rate, Toll-like receptor 2(TLR2) and Bcl-2 expression were examined by flow cytometry. Results The apoptosis rate of virulent (H37Rv) group gradually increased from 1 to 7?days, with the apoptosis rate of 32.2% at 7?days after infection, and then declined after 9 days. Bcl-2 expression of group H37Rv was higher than that of BCG group after 11 days. The TLR2 expression of group H37Rv and group BCG were higher than that in control group, but there was no significant changes. Conclusion Mycobacterium tuberculosis H37Rv strain could apparently induce apoptosis of macrophages and the high expression of Bcl-2 protein could inhibit apoptosis. The apoptosis could be initiated by other potential mechanism but not by TLR2 pathway.

关 键 词：细胞凋亡机制 结核分枝杆菌 宿主 Bcl-2表达 卡介苗(BCG) 巨噬细胞凋亡 Bcl-2蛋白 Toll样受体 细胞凋亡率 信号传导通路 结核杆菌感染 DNA片段化 凝胶电泳检测 Rv感染 不同时期 流式细胞术 正常对照组 H37RV 分子机理 透射电镜 

分 类 号：R52[医药卫生—内科学]