C57BL/6小鼠p38丝裂原活化蛋白激酶通路抑制后抗结核效应  

Anti-Mycobacterium tuberculosis effect of p38 MAPK pathway inhibition in C57BL/6 mice

作　　者：盛青[1] 黄丽军 邹威凤[1] 周强[1] 周晓婷[1] 祝涛 SHENG Qing;HUANG Lijun;ZOU Weifeng;ZHOU Qiang;ZHOU Xiaoting;ZHU Tao(Department of Respiratory Medicine,Guangzhou Chest Hospital,Guangzhou 510095,China;不详)

机构地区：[1]广州市胸科医院呼吸内科,广州510095 [2]宜春市人民医院检验科,江西宜春336000

出　　处：《实用医学杂志》2020年第16期2195-2198,共4页The Journal of Practical Medicine

基　　金：广州市高水平临床重点专科和培育专科建设项目(编号:穗卫函[2019]155号);广东省转化医学创新平台建设项目(编号:省卫函[2018]1254号)。

摘　　要：目的研究p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)通路抑制后小鼠对结核分枝杆菌感染的反应,以进一步阐明该通路在结核病免疫中的作用机制。方法以腹腔注射二甲基亚砜(DMSO)为对照组、注射p38 MAPK抑制剂SB203580(用DMSO溶解)C57BL/6小鼠为观察组,H37RV感染小鼠;30 d后处死小鼠,分析小鼠肺脏、淋巴结、脾脏和肝脏等组织的细菌载量和小鼠肺组织炎症细胞浸润情况和CD4^+、CD8^+、CD4^+IFN-γ^+和CD8^+IFN-γ^+T细胞亚群比例以及细胞因子表达水平。结果观察组小鼠肺、淋巴结、脾脏和肝脏等组织细菌载量(lgCFU/mL)分别为(6.21±0.042)、(5.11±0.07)、(4.91±0.06)和(4.11±0.07),对照组分别为(5.76±0.05)、(4.16±0.05)、(3.96±0.05)和(3.46±0.05),观察组显著高于对照组(P<0.05);观察组小鼠肺组织单核细胞、中性粒细胞、巨噬细胞、CD4^+、CD8^+、CD4^+IFN-γ^+和CD8^+IFN-γ^+T细胞的比例(%)分别为(1.82±0.21)、(4.01±1.68)、(1.92±0.6)、(31.23±2.44)、(59.95±2.98)、(0.48±0.09)和(0.25±0.06),对照组分别为(2.71±0.31)、(7.11±1.88)、(3.42±0.68)、(31.95±1.69)、(59.23±1.38)、(1.22±0.11)和(0.19±0.03),除CD4^+、CD8^+以及CD8^+IFN-γ^+T细胞外,观察组显著低于对照组(P<0.05);相对于内参基因,观察组TNF-α、IL-12P40、IL-17A、IFN-γ、CXCL1、CXCL5和CXCL15分别为(0.52±0.07)、(0.40±0.07)、(0.32±0.082)、(0.46±0.03)、(0.59±0.14)、(0.37±0.21)和(0.41±0.09),对照组分别(1.02±0.11)、(1.03±0.14)、(1.11±0.25)、(1.01±0.08)、(1.17±0.14)、(1.27±0.30)和(1.08±0.26),观察组明显低于对照组(P<0.05)。结论C57BL/6小鼠p38 MAPK通路受到抑制后,可能通过多种免疫路径抑制其抗结核作用。Objective To study the response of mice to Mycobacterium tuberculosis infection after the inhibition of p38 mitogen-activated protein kinase(MAPK)pathway,to further clarify the mechanism of this pathway in tuberculosis immunity.Methods Mice with intraperitoneal injection of dimethyl sulfoxide(DMSO)were chosen as control group,and mice with injection of p38 MAPK inhibitor SB203580(dissolved with DMSO)C57 BL/6 mice as observation group.All mice were infected with H37 Rv.After 30 days,the mice were sacrificed,and the lung,lymph node,spleen and liver were collected for bacterial load counting,and the proportion of inflammatory cells,the proportion of CD4^+,CD8^+,CD4^+IFN-γ^+and CD8^+IFN-γ^+T cell subsets and the expression level of cytokines were measured in the lung tissue.Results The bacterial load(1 gCFU/mL)of lung,lymph node,spleen and liver in the observation group[(6.21±0.04),(5.11±0.07),(4.91±0.06)and(4.11±0.07)respectively]was significantly higher than that in the control group[(5.76±0.05),(4.16±0.05),(3.96±0.05)and(3.46±0.05),respectively].The ratio(%)of lung tissue monocytes,neutrophils,macrophages,CD4^+T cells,CD8^+T cells,CD4^+IFN-γ^+T cells,CD8^+IFN-γ^+T cells in the observation group was(1.82±0.21),(4.01±1.68),(1.92±0.6),(31.23±2.44),(59.95±2.98),(0.48±0.09)and(0.25±0.06)respectively and that in the control group[(2.71±0.31),(7.11±1.88),(3.42±0.68),(31.95±1.692),(59.23±1.38),(1.22±0.11)and(0.19±0.03)respectively].Except the ratio of CD4^+T cells,CD8^+T cells,and CD8^+IFN-γ^+T cells,the ratio of the others was significantly lower than that in the control group(P<0.05).Relative to the reference gene,TNF-α,IL-12 P40,IL-17 A,IFN-γ,CXCL1,CXCL5 and CXCL15 in the observation group were(0.52±0.07),(0.40±0.07),(0.32±0.08),(0.46±0.03),(0.59±0.14),(0.37±0.21)and(0.41±0.09),respectively and those in the control group(1.02±0.11),(1.03±0.14),(1.11±0.25),(1.01±0.08),(1.17±0.14),(1.27±0.30)and(1.08±0.26),respectively(P<0.05).Conclusion The inhabitation of p38 MAPK pathway may

关 键 词：P38丝裂原活化蛋白激酶 结核分枝杆菌 免疫反应 

分 类 号：R378.911[医药卫生—病原生物学] R392.12[医药卫生—基础医学]