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《Chinese Journal of Pathophysiology》 2015-11
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Effect of Mcl-1 signaling pathway blockers on apoptosis of mouse macrophages infected with Mycobacterium tuberculosis H37Rv

ZHANG Yu-qing;WANG Xin-min;WANG Chan;WANG Fei-yu;WANG Xiao-fang;ZHAO Jin;WU Fang;WU Jiang-dong;JI Rong;ZHANG Wan-jiang;ZHANG Le;Department of Pathophysiology,Medical college of Shihezi University;Laboratory of Xinjiang Endemic and Ethnic Diseases, Medical college of Shihezi University;The First Affiliated Hospital, Medical college of Shihezi University;Department of Pathogen Biology & Immunology,Medical college of Shihezi University;Department of Pathology,Medical college of Shihezi University;  
AIM: To explore the effects of Mcl-1 signal pathway blockers on Mcl-1 expression,macrophage apoptosis and Mycobacterium tuberculosis in the model of mice infected with Mycobacterium tuberculosis H37 Rv. METHODS: A mouse infection model was established by intraperitoneal injection of H37 Rv suspension. The signaling pathway blockers AG490,PD98059 and LY294002 for JAK / STAT,MAPK and PI3 K,respectively,were intraperitoneally injected into the mice infected with H37 Rv. Cell acid-fast staining was used to observe whether the mouse peritoneal macrophages infected with H37 Rv were successfully established. Immunocytochemical method was employed to detect Mcl-1 expression in the mouse peritoneal macrophages infected with H37 Rv. The apoptotic rate in each group was measured by flow cytomerty. The scavenging capacity of apoptotic macrophages against H37 Rv was determined by Mycobacterium tuberculosis colony counting. RESULTS: The result of cell acid-fast staining revealed the existence of dispersive arrangement of red short antiacid Mycobacterium tuberculosis within infected macrophages. The result of cell immunocytochemistry showed strongly positive expression of Mcl-1 protein in H37 Rv infection group,AG490 treatment group and LY294002 treatment group,weakly positive expression of Mcl-1 protein in PD98059 treatment group,and negative expression of Mcl-1 protein in control group.The result of flow cytometry found that the macrophage apoptotic rate in H37 Rv infection group was higher than that in control group,while that in PD98059 treatment group was high than that in other groups with statistically significant differences( P 0. 05). The result of Mycobacterium tuberculosis colony counting showed that PD98059 treatment had the most significant inhibitory effect on H37 Rv strain. CONCLUSION: Mcl-1 signaling pathway blockers increase the apoptotic rate of macrophages infected with Mycobacterium tuberculosis H37 Rv and inhibit the growth of Mycobacterium tuberculosis by inhibiting the signaling pathways of JAK / STAT,MAPK and PI3 K,among which the MAPK has the most obvious interfering effect on Mcl-1,and leads to the highest apoptotic rate of infected macrophages and the strongest bacteriostasis.
【Fund】: 国家自然科学基金资助项目(No.81260241)
【CateGory Index】: R378.911
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