地塞米松抑制哮喘大鼠肺组织p38蛋白激酶的表达

Changes of p38 mitogen-activated protein kinase in lung tissue and effects of dexamethasone in asthmatic rats

目的:探讨支气管哮喘大鼠肺组织p38蛋白激酶(p38MAPK)表达的变化以及地塞米松对其影响。方法:复制大鼠哮喘模型,随机分成3组:正常对照组、哮喘对照组和地塞米松(DEX)干预组。分别采用酶联免疫吸附法(ELISA)和蛋白质印迹检测支气管肺泡灌洗液(BALF)IL5含量和肺组织磷酸化p38MAPK表达的变化,并观察气道阻力、BALF中EOS计数以及肺组织病理学变化。结果:哮喘对照组大鼠肺组织磷酸化p38MAPK表达水平及气道阻力、BALF中IL5含量和EOS计数均较正常对照组显著增加(P<0.01);DEX干预组上述指标较哮喘对照组显著降低(P<0.01),肺组织病理学损伤程度明显减轻。肺组织磷酸化p38MAPK表达水平与气道阻力、BALF中IL5含量和EOS计数之间分别呈显著正相关(r=0.77、0.63、0.65,P<0.01)。结论:p38MAPK可能参与了支气管哮喘的发病过程。DEX对哮喘的治疗作用至少部分与抑制磷酸化p38MAPK的表达有关。

AIM: To identify the changes of p38 mitogen-activated protein kinase (p38 MAPK) in lung tissue of asthmatic rats and the effects of dexamethasone on it. METHODS: Ovalbumin (OVA) was injected intraperitoneally and inhaled to produce the asthmatic model. Twenty rats were randomly divided into three groups: control group, asthma group and DEX group. The concentration of IL-5 in BALF and the expression of phospho-p38 MAPK in lung tissue were measured by ELISA and Western blot, respectively. RESULTS: The expression of phospho-p38 MAPK was up-regulated in the lung of asthmatic rats. The injection of DEX intraperitoneally decreased the expression of phospho-p38 MAPK and abolished the increases of airway resistance, the concentration of IL-5 and the number of eosinophil in BALF. Histopathologic damage of lung tissue was alleviated. There were positive correlations between the expression of phospho-p38 MAPK and airway resistance, the concentration of IL-5 and the number of eosinophil in BALF. CONCLUSION: p38 MAPK may play a role in pathological process of asthma. DEX can effectively treat asthma by inhibiting the expression of p38 MAPK.