白三烯受体拮抗剂下调OX40L调控Th9细胞因子改善过敏性哮喘小鼠气道重塑和炎症

Leukotriene receptor antagonist regulates Th9 cytokine to improve airway remodeling and inflammation in mice with allergic asthma via down-regulating OX40L

目的探讨白三烯受体拮抗剂对过敏性哮喘小鼠气道重塑的改善作用及可能机制。方法 30只SPF级BALB/c小鼠随机分成对照组、模型组及孟鲁司特组,每组10只。HE染色观察肺组织形态学变化;Masson染色观察肺组织气道纤维化;ELISA检测支气管肺泡灌洗液IL-4、IFN-γ、IL-9和OVA特异IgE含量;Westernblot检测肺组织OX40L蛋白表达;Westernblot和qRT-PCR检测肺组织TRAF6、 IL-9和IL-9R蛋白及mRNA表达。结果与对照组相比,模型组小鼠肺组织形态学病理变化明显,纤维化增加,支气管肺泡灌洗液IL-4、IL-9和OVA特异IgE含量增加,IFN-γ含量降低,OX40L、TRAF6、IL-9和IL-9R表达水平升高。孟鲁司特改善肺组织形态,降低肺组织气道纤维化,降低支气管肺泡灌洗液IL-4、IL-9和OVA特异IgE含量,增加IFN-γ含量,降低OX40L、TRAF6、IL-9和IL-9R表达水平。结论白三烯受体拮抗剂改善过敏性哮喘小鼠气道重塑和炎症,其作用机制可能与调节OX40L和Th9细胞相关因子表达有关。

Objective To explore the ameliorating effect of leukotriene receptor antagonist on airway remodeling in mice with allergic asthma and its possible mechanism. Methods Thirty SPF BALB/c mice were randomly divided into control group, model group and montelukast group, with 10 mice in each group. HEstaining was used to observe the morphological changes of lung tissue. Masson staining was used to observe the pulmonary tissue airway fibrosis. The levels of IL-4, IFN-γ, IL-9 and OVA-specific IgE in the alveolar lavage fluid were determined by ELISA. The expression of OX40 L protein in lung tissues was detected by Western blot. The protein and mRNA expressions of TRAF6, IL-9 and IL-9 R in lung tissues were detected by Western blot and qRT-PCR. Results Compared with the control group, the pathological changes of lung tissue in the model group were obvious, and the fibrosis was increased. The levels of IL-4, IL-9 and ova specific IgE in BALF was increased, the content of IFNγ was decreased, and The expression levels of OX40 L, TRAF6, IL-9 and il-9 r were increased.Montelukast can improve lung tissue morphology, reduce airway fibrosis, decrease IL-4, IL-9 and ova specific IgE content in bronchoalveolar lavage fluid, and increase the content of IFN-γ, decrease the expression levels of OX40 L, TRAF6, IL-9 and IL-9 R. Conclusion Leukotriene receptor antagonists can improve airway remodeling and inflammation in mice with allergic asthma, and the mechanism may be related to regulating the expression of OX40 L and Th9 cell related factors.