咪喹莫特对哮喘小鼠气道炎症和调节性T细胞的影响

Effects of aerosol imiquimod on the antigen-induced airway inflammation and Foxp3^+ regulatory T cells

目的:观察咪喹莫特对小鼠哮喘模型气道炎症和调节性T细胞Foxp3表达的影响。方法:建立哮喘模型,第0、7、14天分别腹腔注射卵白蛋白(OVA)及其佐剂,自21 d时开始雾化吸入OVA一次,连续7 d,吸入OVA前0.5 h,咪喹莫特组雾化吸入咪喹莫特30 min(1.5 g/L),地塞米松组腹腔注射地塞米松(4 mg/kg)。最后一次OVA雾化吸入后48 h取左下肺组织做HE染色观察肺组织炎症改变;收集支气管肺泡灌洗液(BALF)进行细胞计数、分类和ELISA检测。结果:(1)HE染色显示咪喹莫特组小鼠肺组织炎症程度较哮喘小鼠轻。(2)哮喘组小鼠BALF中嗜酸性粒细胞较正常组显著增加(P<0.01),咪喹莫特组嗜酸性粒细胞比哮喘组显著减少(P<0.01)。(3)哮喘组BALF中IL-5水平较正常组显著升高(P<0.01),咪喹莫特治疗组比哮喘组显著降低(P<0.01)。哮喘组BALF中IL-10水平较正常组显著降低(P<0.01),咪喹莫特治疗组比哮喘组显著升高(P<0.05)。(4)哮喘组脾脏组织Foxp3+细胞数量较正常组减少,咪喹莫特组与地塞米松组较哮喘组增加(P<0.01)。结论:雾化吸入咪喹莫特可在一定程度上增加Foxp3+细胞数量,减轻哮喘小鼠的气道炎症。

AIM ： To observe the effects of aerosol imiquimod on the antigen-induced airway inflammation and Foxp3 ＋ regulatory T cells. METHODS ： Thirty-two female BALB/c mice were randomly divided into four groups： control,asthma model,imiquimod and glucocorticoid treatment groups.Asthma was induced by OVA administration in the asthma model,imiquimod and glucocorticoid treatment groups.Imiquimod and dexamethasone were administered to immunized mice before antigen challenge.After 48 hrs of the last challenge,the mice were killed and bronchial alveolar lavage fluid（BALF） was collected to count the number of eosinophil and to measure the levels of IL-5 and IL-10.The lung tissues of inferior lobe of the left lung were obtained for the observation of lung pathological change.The spleen CD 4 ＋T cells were isolated and collected.The proportion of CD 25 ＋Foxp3 ＋T cells in the CD 4 ＋T cells were determined with flow cytometry. RESULTS ：（1）Imiquimod attenuated the airway inflammation of asthmatic mice.（2）In imiquimod and dexamethasone treatment groups eosinophil counts increased by OVA was decreased in BALF of mice.（3）In BALF of imiquimod treatment mice,the level of IL-5 increased by OVA was decreased and IL-10 decreased by OVA was increased.（4）The number and proportion of CD 4 ＋CD 25 ＋ Foxp3 ＋T cells were higher in control and treatment groups than that in the asthmatic group. CONCLUSION ： Imiquimod aerosol inhalation may inhibit antigen-induced airway inflammation and the number and proportion of CD 4 ＋CD 25 ＋Foxp3 ＋T cells.