FTY-720通过S1P1受体调节哮喘小鼠气道炎症

FTY-720 regulated airway inflammation in asthmatic mice via S1P1 receptor

目的:探究S1P1对哮喘小鼠气道炎症的影响,并研究FTY-720的作用机制是否与S1P1/WNT1/RAC1/P38-MAPK信号通路有关。方法:30只雄性BALB/c小鼠随机分为3组,OVA建立小鼠哮喘模型,24 h后检测小鼠病理组织学变化;小鼠支气管肺泡灌洗液(BALF)中嗜酸性粒细胞数量,中性粒细胞数量、淋巴细胞数及细胞炎症因子水平;检测小鼠血清中IgE含量;Western blot检测小鼠肺组织S1P1、WNT1/RAC1/P38-MAPK等蛋白表达。结果:FTY-720可显著降低哮喘小鼠肺内炎症因子IL-1、IL-4、IL-5及血清中IgE水平,降低WNT1/RAC1/P38-MAPK等蛋白含量,抑制哮喘。结论:S1P1可参与哮喘发生并通过WNT1/RAC1/P38-MAPK通路改善哮喘小鼠气道炎症。

Objective:To explore effect of S1P1 on airway inflammation in asthmatic mice,and to investigate whether the mechanism of action of FTY-720 was related to S1P1/WNT1/RAC1/P38-MAPK signaling pathway.Methods:Thirty male BALB/c mice were randomly divided into four groups,established asthma model by OVA.Histopathological changes of mice were detected after 24 h.Numbers of eosinophils,neutrophils,lymphocytes and cellular inflammatory factors in bronchoalveolar lavage fluid(BALF)of mice were detected;IgE content in serum of mice was detected;Protein expressions of S1P1,WNT1/RAC1/P38-MAPK in lung tissues of mice were detected by Western blot.Results:FTY-720 significantly decreased levels of inflammatory factors IL-1,IL-4,IL-5 and IgE in lung and WNT1/RAC1/P38-MAPK protein levels of asthmatic mice,and inhibited asthmatic inflammation.Conclusion:S1P1 can participate in development of asthma and ameliorate airway inflammation in asthmatic mice through WNT1/RAC1/P38-MAPK pathway.