咪喹莫特对小鼠哮喘模型气道炎症和STAT6表达的影响  

Effects of imiquimod on airway inflammation and STAT6 expression in mouse models of asthma

作　　者：金淑贤[1] 殷凯生[1] 卞涛[1] 陈子庆[2] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,江苏南京210029 [2]南京医科大学第一附属医院中心实验室

出　　处：《第四军医大学学报》2006年第6期548-552,共5页Journal of the Fourth Military Medical University

摘　　要：目的观察咪喹莫特对小鼠哮喘模型气道炎症和肺组织信号转导与转录激活因子1(STAT1)和STAT6表达的影响.方法建立哮喘模型,自14d时雾化吸入OVA前0.5h,干预组分别雾化吸入咪喹莫特30min及ip地塞米松.OVA雾化结束后24h取左上叶肺组织做HE染色观察肺组织炎症改变;收集肺泡灌洗液进行细胞计数和分类;用免疫组化和West blot方法检测肺组织STAT1和STAT6的表达;用逆转录-聚合酶链反应半定量检测肺组织STAT1,STAT6,IL-4,eotaxin和IFN-γmRNA表达水平.结果①HE染色示地塞米松组和咪喹莫特组小鼠肺组织炎症程度较哮喘小鼠减轻.②哮喘组小鼠BALF中细胞总数及各种炎症细胞较正常组显著增加,咪喹莫特治疗组嗜酸性粒细胞、淋巴细胞比哮喘组明显减少(P<0.01).③STAT1和STAT6均在气道上皮细胞表达,哮喘组肺组织STAT1和STAT6表达较正常组增强,咪喹莫特组STAT1表达与哮喘组无明显区别,较正常组增加.④哮喘组小鼠肺组织STAT1,STAT6,eotaxin,IL-4mRNA表达较正常组增强(P<0.01),IFN-γmRNA表达减少,咪喹莫特组STAT1mRNA表达与哮喘组无明显区别,STAT6,eotaxin和IL-4mRNA的表达较哮喘组降低,较正常组增加,IFN-γmRNA表达较哮喘组增加,但低于正常组.结论雾化吸入咪喹莫特可在一定程度上减轻哮喘小鼠的气道炎症,抑制肺组织STAT6蛋白和mRNA的过度表达.AIM： To observe the effects of aerosol imiquimod on the antigen-induced airway inflammation and the expressions of Th2-type chemokines Eotaxin, macrophage-derived chemokine （MDC） and thymus and activation regulated chemokine （TARC） in mouse models of asthma. METHODS： Imiquimod and dexamethasone were administered to immunized mice before antigen challenge. At 24 h after the final OVA inhalation, the left superior lung tissue was taken, HE stained and the changes of inflammation were observed. Bronchial alveolar lavage fluid （BALF） was collected to count the number of cells and classify them. The expressions of signal transducers and activators of transcription 1 （ STAT1 ） and signal transducers and activators of transcription 6 （STAT6） in lungs were detected by immunohistochemistry and western blot. The mRNA expressions of STAT1, STAT6, IL-4, eotaxin and IFN-γ in lungs were examined by reverse transcriptase-polymerase chain reaction. RESULTS： ① Imiquimod and dexamethasone attenuated the airway inflammation of asthmatic mice. ② Imiquimod decreased the totol cell counts, EOS and lymphocyte counts in BALf. ③ The expressions of STAT1 and STAT6 were mainly on the bronchial epithelium. STAT1 and STAT6 proteins and mRNA levels increased in lung tissues in asthma group. Imiquimod significantly reduced STAT1 and STAT6 protein and mRNA expression. Dexamethasone significantly reduced the levels of STAT6 protein and mRNA, but failed to inhibit the expression of STAT1. ④ Imiquimod modulated the Th1/Th2 response by enhancing Thl cytokine IFN-γ mRNA and inhibiting the Th2 cytokine IL-4 mRNA expression in lung tissues. CONCLUSION： Imiquimod aerosol inhalation may inhibit antigen-induced airway inflammation and decrease the over expression of STAT6 protein and mRNA in asthmatic mouse but has no influence on STAT1 expression.

关 键 词：哮喘 信号转导与转录激活因子1 信号转导与转录激活因子6 咪喹莫特 

分 类 号：R562.2[医药卫生—呼吸系统]