肺结核肺组织干扰素-γ表达与其病理损伤间的关系研究

Association between IFN-γ expression and pathological damage of lung tissue during pulmonary tuberculosis

目的:研究细胞因子干扰素-γ(IFN-γ)在肺组织中的表达变化与肺组织病理损伤间的相互关系,为肺结核的防治提供参考。方法:毒性结核分枝杆菌H37Rv尾静脉注射BALB/c小鼠建立肺结核动物模型,分别于感染后0(未感染)、2、4、6、8周末,进行肺组织细菌载荷量计数及组织病理观察,免疫组织化学染色检测IFN-γ、IL-2及TNF-α在肺组织的表达。结果:MTB感染后2周末,IFN-γ、IL-2及TNF-α的阳性细胞百分比较0周时均显著升高,感染后6周末(9.25%)至8周末(5.67%),IFN-γ阳性细胞百分比显著下降(P<0.01)。而该时期TNF-α及IL-2的表达均有下降趋势,但与感染后2周或4周时无明显差异(P>0.05)。感染后8周末,肺组织细菌载荷量(8.43)及肺组织病理分数(17)较感染6周时均显著升高(P<0.01)。结论:MTB感染早期,肺组织IFN-γ、TNF-α及IL-2均呈较高表达,对肺组织具有较强的保护作用。MTB持续感染期,IFN-γ表达量下降明显加剧肺组织损伤。

Objective To investigate the relationship between the expression of IFN-γ, IL-2 and TNF-α and pathological damage of lung tissue, and to provide reference values for protection and treatment of pulmonary tuberculosis. Methods BALB / c mice models of pulmonary tuberculosis were established by infection with Mycobacterium tuberculosis H37Rv through the caudal vein. At 0（not infected）,2,4,6W and 8W after infection, the bacterial loads in the lung were performed and the pathological damage of the lung was evaluated, respectively. At the same time, the expression of IFN-γ,IL-2 and TNF-α-positive cells in the lung tissues was detected by immunohistochemistry. Results Two weeks after infection, the expression of IFN-γ, IL-2 and TNF-α positive cells was obviously increased compared with those at 0 week. The proportion of IFN-γ-positive cells were obviously decreased at 6 weeks（9.25%） to 8 weeks（5.67%） after infection with Mycobacterium tuberculosis H37Rv. At the same stage, there is a limited decrease tendency of TNF-α and IL-2 expression compared with those at 4 weeks after infection, and there was no significant difference compared with those at 2W or 4W after infection. At 8 weeks after infection, the bacterial loads（8.43） in the lung and the scores（17） of pathological damage were significantly increased compared with those at 6 weeks after infection. Conclusion The high expression of IFN-γ, IL-2 and TNF-α protect lung tissues against MTB infection at the early stage. The decrease of IFN-γ expression is responsible for serious damage of the lung tissues in the persistent infection.