p38蛋白激酶抑制剂SB203580对支气管哮喘小鼠气道炎症和Th2类细胞因子的影响

目的观察特异性p38蛋白激酶(p38 MAPK)抑制剂SB203580对哮喘小鼠气道炎症和Th2类细胞因子的影响。方法BALB/c小鼠30只随机分成3组,即正常对照组、哮喘模型组和SB203580干预组。通过原位分子杂交和酶联免疫吸附法(ELISA)检测肺组织IL-4、IL-5 mRNA和支气管肺泡灌洗液(BALF)中白细胞介素(IL-4、IL-5)含量的变化,并观察BALF中炎症细胞和肺组织病理学改变。结果哮喘模型组小鼠BALF中炎症细胞计数和IL-4、IL-5含量以及肺组织IL-4、IL-5mRNA的表达较正常对照组明显升高,差异具有显著性(P<0.01);SB203580干预组小鼠上述指标较哮喘模型组小鼠明显降低,差异亦具有显著性(P<0.01),肺组织病理学改变明显减轻。结论SB203580能降低气道炎症细胞的聚集和炎症介质的表达。抑制p38 MAPK的活性可能成为哮喘治疗的新途径。

Effects of p38 MAPK kinase inhibitor SB203580 on the airway inflammation and Th2 cytokines in asthmatic mice

Aim To explore the effects of SB203580,a special inhibitor of p38 mitogen-activated protein kinase(p38 MAPK),on the airway inflammation and Th2 cytokines,interleukin 4(IL-4) and IL-5,in asthmatic mice.Methods Thirty mice were randomly divided into 3 groups: normal control,asthmatic group and SB203580 group.The expression of IL-4 mRNA and IL-5 mRNA in lung tissue and IL-4 and IL-5 protein in bronchial alveolar lavage fluid(BALF) were detected using in situ hybridization and ELISA,respectively.The number of inflammatory cells in BALF and histopathological changes were observed.Results The number of inflammatory cells and the concentrations of IL-4 and IL-5 in BALF,and the expression of IL-4 mRNA and IL-5 mRNA in lung tissue were higher in the asthmatic mice than in the normal control mice(P<0.01);and those in SB203580-treated mice were lower than in the asthmatic mice(P<0.01).The histopathological damage was alleviated in the SB203580 group mice as compared to the asthmatic group mice.Conclusions SB203580 can inhibit the aggregation of airway inflammatory cells and the expression of inflammatory cytokines.The inhibition by p38 MAPK may be a new way to treat asthma.