白三烯受体拮抗剂介导NLRP3/Caspase-1/IL-1β信号通路改善支原体肺炎小鼠Th1/Th2免疫失衡

Leukotriene receptor antagonist mediates NLRP3/Caspase-1/IL-1β signaling pathway to improve Th1/Th2 immune imbalance in mice with mycoplasma pneumonia

目的 探究白三烯受体拮抗剂对支原体肺炎小鼠Th1/Th2免疫的影响及可能机制。方法 30只BALB/c小鼠随机分为对照组(Control组)、肺炎支原体感染组(MP组)和白三烯受体拮抗剂孟鲁斯特(MK组),通过滴鼻接种菌液建立支原体肺炎小鼠模型。取材后对各组小鼠计算肺湿重指数;HE染色观察肺组织病理变化;ELISA法检测肺泡灌洗液中IL-1β、IL-12、IFN-γ、TNF-α含量;TUNEL法检测肺组织细胞凋亡情况;流式技术检测外周血CD4^(+)/CD8^(+)水平;Western blot法检测肺组织NLRP3、pro-caspase1、pro-IL1β的表达水平。结果 白三烯受体拮抗剂改善支原体肺炎小鼠肺脏损伤,抑制IL-1β、IL-12、IFN-γ、TNF-α的分泌,抑制细胞凋亡,改善Th1/Th2免疫失衡,下调NLRP3、pro-caspase1、pro-IL1β的表达。结论 白三烯受体拮抗剂通过介导NLRP3/Caspase-1/IL-1β信号通路改善Th1/Th2免疫失衡,降低肺脏损伤。

Objective To explore the effects of leukotriene receptor antagonists on Th1/Th2 immunity in mice with mycoplasma pneumonia and its possible mechanism. Methods Thirty BALB/c mice were randomly divided into control group(Control group), mycoplasma pneumoniae infection group(MP group) and leukotriene receptor antagonist montelukast(MK group). Mice model of mycoplasma pneumonia was established by nasal drip inoculation. After collecting the samples, the wet weight index of the lungs of mice of each group was calculated. The pathological changes of lung tissue was observed by HE staining. The contents of IL-1β, IL-12, IFN-γand TNF-α in the alveolar lavage fluid was detected by ELISA. Cell apoptosis of lung tissue was detect by TUNEL. Levels of CD4^(+)/CD8^(+) in peripheral blood was detected by flow cytometry. The expression of NLRP3, pro-caspase1, pro-IL1β in lung tissue was detected by Western blot. Results Leukotriene receptor antagonist improves lung injury in mice with mycoplasma pneumonia, inhibits the secretion of IL-1β,IL-12, IFN-γ and TNF-α, inhibits cell apoptosis, improves Th1/Th2 immune imbalance, and down-regulates the expression of NLRP3, pro-caspase1 and pro-IL1β. Conclusion Leukotriene receptor antagonists mediate the NLRP3/Caspase-1/IL-1β signaling pathway to improve Th1/Th2 immune imbalance and reduce lung damage.