目的:研究支气管哮喘不同时期细胞外信号调节激酶(External signal regulated kinase,ERK)的磷酸化与c-Fos表达,以探讨ERK信号转导途径在支气管哮喘气道重塑中的作用。方法:复制大鼠哮喘模型,随机分为对照组(包括4周、8周及12周对照组)、哮喘组(包括4周、8周及12周哮喘组),图像分析软件测定支气管壁厚度(Wat)和平滑肌厚度(Wam),免疫组化测定肺组织磷酸化的ERK(Phospho-ERK,P-ERK)与c-Fos表达,免疫印迹法测定磷酸化的ERK水平,直线相关分析法显示Wat和Wam与P-ERK的相关性。结果:各哮喘组Wat和Wam,P-ERK和c-Fos的平均吸光度均显著高于相应对照组(P均〈0.01);各哮喘组磷酸化的ERK水平均显著高于相应对照组(其中A12也与C8组比)(P〈0.01);Wat、Wam与P-ERK平均吸光度均呈显著正相关性(P〈0.01)。结论:ERK磷酸化水平和c-Fos在哮喘大鼠均增加,ERK信号转导途径在支气管哮喘气道重塑中起重要作用。
Objective: To study phosphorylafion of ERK and expressions of c-Fos, and to explore the role of external signal regulated kinase (ERK) signal transduction pathway in asthma airway remodeling . Methods:Asthma model was developed,The rats were randomly divided into control groups( including 4 weeks ,8weeks and 12 weeks control) and asthma groups (including 4 weeks ,8weeks and 12 weeks asthma groups). Total brochial wall thickness (Wat) and smooth muscle thickness(Warn) were measured by image anal- ysis system. Phospho-ERK(P-ERK) and c-Fos were detected by immunohistochemistry technique;lung tissue extracts were analyzed for phosphorylation of ERK by Western blot. the correlation between Wat and P-ERK,Wam and P-ERK. Results:Wat and Warn,mean optical density( by immunohistochemistry) of P-ERK and c-Fos in asthma groups were all significantly higher than those in corresponding control groups (P 〈0. 01, respectively) ;the level of P-ERK in asthma groups were significantly higher than that in corresponding control groups (while A12 group also compared with C8 group) (P 〈 0. 01 respectively) ;Wat and Warn positively correlated with mean optical density of P-ERK. Conclusion:The level of P-ERK and c-Fos increase in asthma rats, ERK signal transduction pathway palys an important role in asthma airway remodeling.