布地奈德对哮喘小鼠T淋巴细胞亚群及相关细胞因子的影响

Effect of budesonide on T lymphocyte subsets and related cytokines in mice with asthma

目的 探讨雾化吸入原研和国产布地奈德对支气管哮喘(哮喘)小鼠T淋巴细胞亚群及相关细胞因子的影响。方法 24只BALB/c小鼠随机均分为对照组(A组)、哮喘模型组(B组)、国产布地奈德混悬液治疗组(C组)和原研布地奈德混悬液治疗组(D组)。采用过碘酸希夫和HE染色观察小鼠肺组织病理学改变,ELISA法检测肺泡灌洗液中IL-4、IL-5、IL-10、IL-13、IL-17和IFN-γ水平,流式细胞术检测T淋巴细胞亚群的比例。结果 与A组相比,B组IL-10和IFN-γ水平、Th1和调节性T淋巴细胞(Treg细胞)比例以及Th1/Th2细胞比值较低(P<0.05),IL-4、IL-5、IL-13、IL-17水平以及Th2和Th17细胞比例较高(P<0.05),B组小鼠肺组织中上皮细胞增生,支气管管腔狭窄,炎症细胞浸润;C组和D组经布地奈德治疗后上述各指标均得到有效改善(P<0.05),并且组间各指标比较差异无统计学意义(P>0.05)。结论 国产和原研布地奈德均可能通过激活Th1和Treg细胞,抑制Th2和Th17细胞及相关细胞因子来调控T淋巴细胞亚群失衡,从而有效控制哮喘。

Objective To investigate the effect of nebulized inhalation of original and domestic budesonide on T lymphocyte subsets and related cytokines in the mice with asthma.MethodsTwenty-four BALB/c mice were equally randomized into four group of A(normal control),B(asthma model),C(inhaled with domestic budesonide) and D(inhaled original budesonide).The pathological changes of lung tissues were observed by PAS and HE staining.The levels of IL-4,IL-5,IL-10,IL-13,IL-17 and IFN-γ in the bronchoalveolar lavage fluid were determined by ELISA method.The proportions of T cell subsets were detected by flow cytometry.Results Compared with group A,the levels of IL-10 and IFN-γ,proportions of Th1 and Treg cells and ratio of Th1 to Th2 cells were lower(P<0.05),the levels of IL-4,IL-5,IL-13 and IL-17 and proportions of Th2 and Th17 cells were higher(P<0.05),and the hyperplastic epithelial cells, narrow bronchial lumen and infiltrative inflammatory cells were found in group B,which were all significantly improved after nebulized inhalation of budesonide in groups of C and D(P<0.05).However, there were no statistical differences in the above indexes between groups of C and D(P>0.05).Conclusion Both domestic and original budesonide can effectively control asthma by activating Th1 and Treg cells, inhibiting Th2 and Th17 cells and related cytokines to regulate the imbalance of T lymphocyte subsets.