血红素加氧酶1对哮喘小鼠Th1/Th2比值及ILC2的调节作用

The regulatory effect of heme oxygenase 1 on Th1/Th2 ratio and ILC2 in asthmatic mice

为探究血红素加氧酶1(heme oxygenase 1,HO-1)对哮喘小鼠Th1/Th2比值及ILC2百分比的影响,选用屋尘螨(house dust mite,HDM)致敏、激发C57BL/6小鼠制备以嗜酸性粒细胞(eosinophil,EOS)浸润为主的小鼠哮喘模型,给予氯化高铁血红素(hemin)诱导HO-1高表达。观察肺脏组织病理学变化,检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中EOS百分比及肺脏组织炎性因子水平以评估哮喘小鼠气道炎症程度;Western blotting检测肺脏组织HO-1蛋白表达量;FACS分析肺脏组织Th1、Th2及ILC2百分比。结果显示,HDM致敏、激发后小鼠肺脏炎性因子分泌增加,气道EOS浸润增多,肺脏Th1/Th2比值失衡,同时ILC2百分比增加(有P<0.05)。而hemin诱导的HO-1高表达能够缓解上述炎症反应过程,恢复Th1/Th2平衡,同时逆转ILC2百分比(有P<0.05)。以上结果表明,上调HO-1表达能够抑制HDM所致过敏性哮喘气道炎症反应,这一作用可能是通过降低ILC2百分比并维持Th1/Th2平衡实现的。

To explore the regulatory effect of heme oxygenase 1(HO-1)on Th1/Th2 ratio and ILC2 percentage in eosinophilic asthma mouse model,C57 BL/6 mice were sensitized and challenged with house dust mite(HDM),and treated by hemin to upregulate HO-1 expression.Lung tissue pathological analysis,the percentage of eosinophil(EOS)in bronchoalveolar lavage fluid(BALF)and the levels of lung inflammatory factors were measured to evaluate the airway inflammation degrce in asthmatic mice;The HO-1 expression was determined by Western blotting,and the percentages of Th1,Th2 and ILC2 in the lung tissue were detected by FACS.The results showed that the levels of inflammatory cytokines were increased and airway eosinophil infiltration was aggravated,concomitant with imbalanced Th1/Th2 ratio and increased percentage of ILC2 in HDM-induced mice(some P<0.05).However,the characterization described above was reversed by HO-1 overexpression induced by hemin(some P<0.05).This study indicates that up-regulation of HO-1 expression can inhibit HDM-induced allergic airway inflammation,which may be achieved by restoring Th1/Th2 balance and reducing ILC2 percentages.