TLR2-p38MAPK信号通路在小鼠肺炎衣原体肺炎中的表达及意义

目的通过建立小鼠肺炎衣原体感染的模型,探讨小鼠感染肺炎衣原体后,其信号通路Toll样受体2（TLR2）-p38蛋白激酶（p38MAPK）中TLR2 mRNA和p38MAPK mRNA的表达变化及其信号通路抑制剂对其影响以及炎症介质表达变化的意义。方法使用TLR4基因缺失小鼠（C3H/HeJ）72只,随机分为正常组、肺炎衣原体感染组、肺炎衣原体感染加特异性p38MAPK抑制剂SB203580干预组,分别按接种后1、4、7及14 d各分4组。正常组鼻内接种2SP缓冲液,感染组鼻内接种肺炎衣原体;干预组在感染肺炎衣原体后即在腹腔注射SB203580,分别在预定的时间处死,取肺脏组织应用逆转录-聚合酶链反应（RT-PCR）半定量方法检测肺组织TLR2 mRNA和p38MAPK mRNA的表达变化,用酶联免疫吸附法（ELISA）测定TNF-α的含量。结果与正常组比较,感染肺炎衣原体后小鼠肺组织TLR2 mRNA和p38MAPK mRNA表达迅速升高,以第4 d和第7 d最明显,其中TLR2mRNA在第7 d表达量明显高于正常组（7.24±1.78）mg/L比（0.64±0.14）mg/L],p38MAPKmRNA在第4 d表达量明显高于正常组（9.267±1.813）mg/L比（3.734±0.946）mg/L],14 d以后感染开始减轻。其相应的肺组织TNF-α含量表达也升高,并明显高于正常组,以第4 d为高峰（77.29±9.66）pg/mg。给予SB203580抑制剂后TLR2 mRNA和p38MAPK mRNA表达明显减弱,以第4 d和第7 d明显,其中TLR2 mRNA在第7 d为（0.269±0.09）mg/L,p38 MAPK mRNA在第4 d为（0.002±0.001）mg/L,其相应的肺组织TNF-α含量表达与感染组比较也明显降低,以第4 d（25.76±3.49）pg/mg明显。结论小鼠感染肺炎衣原体后,可引起TLR2-p38 MAPK信号通路的活化,引起细胞因子的释放。SB203580对TLR2-p38 MAPK信号通路有明显的抑制作用,并能抑制炎症介质的释放,表明肺炎衣原体感染与TLR2-p38MAPK的信号通路密切相关。

The Expression and Significance of Toll-Like Receptor2-p38 MAPK Pathway in Chlamydia Pneumoniae Infection of Mice

Objective To investigate whether Chlamydia pneumoniae alters the expression of TLR2 mRNA and p38 MAPK mRNA in mice with Chlamydia pneumoniae infection in TLR2-p38 MAPK-dependent pathway,subsequently leading to the rele as e of cytokines.Methods Seventy-two male C3H/HeJ mice were ra ndomly divided in to three groups as follow:a normal control group,a C.pneumoniae-inoculated group,and a C.pneumoniae-inoculated with SB203580 treatment group.The mice in the th r ee groups were sacrificed on 1st,4th,7th,14th day...