不同亚型Smads信号蛋白在慢性支气管哮喘小鼠肺组织表达的意义

The Significance of Different Subtypes of Smads Signaling Proteins in Lung Tissue of Mice with Chronic Bronchial Asthma

目的观察慢性支气管哮喘小鼠肺组织内Smads不同亚型信号蛋白的表达,探索不同亚型Smads蛋白及其传导的信号通路在慢性支气管哮喘小鼠慢性气道炎症及气道重塑过程中的作用。方法建立急性哮喘及慢性哮喘小鼠动物模型,行肺组织病理切片,分别以免疫组织化学法和Western-blot法检测肺组织Smad 1,3,4,5,7的表达。结果慢性哮喘组小鼠的肺组织病理可见杯状细胞顶部空泡化明显,支气管黏膜下及肺实质血管旁多种炎症细胞浸润,支气管黏膜皱襞明显增多,上皮细胞增生紊乱。免疫组织化学法和Western-blot法检测结果显示,急性哮喘组小鼠的R-Smads(Smad 1,3,5)及Co-Smad(Smad 4)表达较正常对照组均明显升高(P<0.05),I-Smad(Smad 7)表达减少(P<0.05);慢性哮喘组BMP/Smads信号通路Smads蛋白(Smad 1,5)表达较急性哮喘组降低(P<0.05),Smad 7较急性哮喘组明显升高(P<0.05),而TGF-β1/Smads信号通路Smads蛋白(Smad 3)及Co-Smad(Smad 4)表达则较急性哮喘组进一步升高(P<0.05)。结论转导不同上游信号分子的Smads蛋白所介导的信号通路在慢性支气管哮喘活化状态不同,TGF-β1/Smads信号通路在慢性支气管哮喘活化,BMP/Smads信号通路在急性哮喘中活化,但在慢性哮喘中活化降低。

Objective To observe the expression of different subtypes of Smads in the lung tissue of mice with chronic bronchial asthma,and to explore the role of different subtypes of Smads protein and its signaling pathway in chronic airway inflammation and airway remodeling in mice with chronic bronchial asthma.Methods Mouse models of acute asthma and chronic asthma were established and lung histopathological sections were performed.The expressions of Smad 1,3,4,5,and 7 in lung tissues were detected respectively by immunohistochemistry and Western-blot.Results In the chronic asthma group,the top vacuolation of goblet cells was obvious;various inflammatory cells infiltrated under the bronchial mucosa and near the pulmonary parenchyma vessels;the bronchial mucosa plica was significantly increased;the epithelial cell had proliferative disorder.Immunohistochemistry and Western-blot results showed that the expressions of R-Smads,including Smad 1,3,5 and Co-Smad,including Smad 4 in the acute asthma group were significantly higher than those in the normal control group(P<0.05),but the expression of I-Smad,including of Smad 7 were decreased(P<0.05).In the chronic asthma group,the expressions of Smad 1 and 5 in the BMP/Smads signaling pathway was lower than that in the acute asthma group(P<0.05);Smad 7 was significantly higher than that in the acute asthma group(P<0.05);and the expression of Smad 3 in the TGF-β1/Smads signaling pathway and co-smad(Smad 4)was higher than that in the acute asthma group(P<0.05).Conclusion The signaling pathways mediated by Smads proteins in different advanced signals are dissimilar in the active state of the chronic bronchial asthma,and the TGF-β1/Smads signaling pathway is activated in the chronic bronchial asthma.The BMP/Smads signaling pathway is activated in acute asthma,but decreases in chronic asthma.