摘要
目的观察阻断髓样细胞白血病-1(Mcl-1)表达的信号通路对H37Ra感染小鼠的影响,从而探讨Mcl-1干预在此过程中的作用。方法制备好结核分枝杆菌H37Ra的菌悬液后,将其感染BALB/c小鼠,再用Mcl-1信号通路阻断剂AG490、PD98059、LY294002分别腹腔注射结核感染的小鼠模型,并同时设立相应的对照组。应用倒置显微镜观察巨噬细胞形态、TUNEL技术检测阻断剂应用后巨噬细胞的凋亡率、细胞免疫化学分析Mcl-1的表达、HE染色观察小鼠脏器的病理损伤变化。结果阻断剂处理后的H37Ra感染组凋亡率与空白对照组相比,均出现不同程度的升高,其中PD98059处理组凋亡率最高(P <0.05)。阻断剂PD98059处理后,H37Ra在巨噬细胞内的菌落数量明显减少,小鼠肝、肺、脾、肾的病理损害程度明显减轻(P <0.05)。结论阻断Mcl-1表达的信号通路可以显著促进结核感染的小鼠巨噬细胞的凋亡,减少结核杆菌在宿主巨噬细胞内的存活,减轻结核感染对小鼠脏器的病理损伤。而MAPK信号通路是此过程中调控Mcl-1表达的主要通路,且PD98059为其特异性抑制剂。
Objective To investigate the effect of inhibitors of Mcl?1 signaling on H37Ra-infected mice.Methods After the preparation of bacterial suspension of mycobacterium tuberculosis H37Ra,BALB/c mice were infected,then Mcl-1 signaling blockers AG490,PD98059 and LY294002 were intraperitoneally injected,respectively.The morphology of macrophages was observed by the inverted microscope,the apoptosis of macrophages was detected by TUNEL assay,Mcl-1 expression was detected by immunochemical analysis,and the pathological chang?es of mouse organs were detected by HE staining.Results Compared with the blank control group,the apoptosis of the H37Ra-infected group treated with blockers was increased in varying degrees.The apoptosis in PD98059 treatment group was the highest(P<0.05).In PD98059 blocker?treated mice,the number of colonies of H37Ra in macrophages was significantly reduced,and the degrees of pathological damage of liver,lung,spleen,kidney organs in mice were significantly reduced(P<0.05,respectively).Conclusions Blocking Mcl-1 expression can significantly promote the apoptosis of mouse peritoneal macrophages infected with MTB,reduce the survive of mycobacterium tuberculosis colonies in host macrophages,and reduce the pathological damage of mice organs caused by MTB infection.While MAPK signaling pathway is the main pathway regulating Mcl?1 expression in this process.
作者
王新敏
王小芳
卢洋
杨菩
韩玲
王英姿
张万江
章乐
WANG Xinmin;WANG Xiaofang;LU Yang;YANG Pu;HAN Lin;WANG Yingzi;ZHANG Wanjiang;ZHANG Le(Department of Urinary Surgery,the First Affiliated Hospital of Shihezi University,Medical College of Shihezi University,Shihezi 832002,China)
出处
《实用医学杂志》
CAS
北大核心
2018年第18期3011-3015,共5页
The Journal of Practical Medicine
基金
国家自然科学基金资助项目(编号:81660330)
关键词
结核
Mcl-1信号通路
腹腔巨噬细胞
细胞凋亡
tuberculosis
Mcl-1 signals pathway
mouse peritoneal macrophages
cell apoptosis
