目的 探讨特异性p38蛋白激酶(p38 MAPK)抑制剂SB203580对小鼠感染肺炎衣原体后细胞因子变化.方法 使用TLR4基因缺失(C3H/HeJ)小鼠90只,随机分为正常组、感染组和SB203580组,每组再分别按0、1、4、7、14 d分成5小组.正常组鼻内接种二磷酸蔗糖缓冲液,感染组鼻内接种肺炎衣原体约4.0×106 IFU/ml,SB203580组在感染肺炎衣原体后腹腔注射SB203580(100 mg/kg).分别在接种后第0天,第1天、第4天、第7天、第14天预定的时间处死小鼠,取肺组织分别采用Western blot法测p38 MAPK蛋白的表达,用酶联免疫吸附法检测肺组织中肿瘤坏死因子α(TNF-α)、白介素1(IL-1)的表达,同时观察各组小鼠肺组织病理变化.结果 感染组肺组织中TNF-α、IL-1的表达水平在各时间点均高于正常组(P＜0.05或P＜0.01),并在第4天出现高峰,14天以后开始下降.SB203580组肺组织中细胞因子TNF-α、IL-1的表达水平在各时间点均低于感染组(P＜0.05或P＜0.01).同时,SB203580组p38 MAPK蛋白表达强度弱于感染组.结论 p38 MAPK参与小鼠感染肺炎衣原体的炎症反应,特异性p38 MAPK抑制剂SB203580能抑制小鼠感染肺炎衣原体后的细胞因子表达,减轻炎症反应.%Objective To investigate the effect of SB203580,a specific inhibitor of p38 mitogen activated protein kinase (MAPK),on cytokines in mice infected with Chlamydia pneumoniae.Methods Ninety male C3H/HeJ mice were randomly divided into three groups:normal group,infected group and SB203580 group.The infected group was intranasally inoculated with 4.0×106 IFU /ml of Chlamydia pneumoniae.Then SB203580 group was intraperitoneally injected with SB203580(100 mg/kg).Mice in the three groups were killed and lung tissue samples were taken after 0,1,4,7,14 days,separately,p38 MAPK expression was measured by Westen blot.The concentrations of tumor necrosis factor-α(TNF-α) and interleukin-1(IL-1) in the lung tissue were measured by enzyme linked immunosorbent assay.Results The expressions of TNF-α,IL-1 in the lung tissue of infected group at different time points,which appeared peak at 4th day,then decreased after 14 days,were all higher than those of normal group(P＜0.05 or P＜0.01).The expressions of TNF-α,IL-1 in the lung tissue of SB203580 group at different time points were lower than those of infected group(P＜0.05 or P＜0.01).The expression level of p38 MAPK in SB203580 group was less than that in infected group.Conclusions p38 MAPK is involved in inflammatory response of the mice with Chlamydia pneumoniae.SB203580 can restrain the expression of the cytokines and decrease inflammatory response in mice with Chlamydia pneumoniae.
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