【摘要】 目的探讨血红素加氧酶-1(heme oxygenase-1,HO-1)介导1型T调节细胞(type1T regulatory cells,Tr1)在哮喘动物模型中的免疫调节作用。方法用卵清蛋白(ovalbumin,OVA)致敏、激发C57B6小鼠建立哮喘模型,并在致敏、激发阶段分别经血红素(hemin)和锡-原卟啉(Sn-protoporphyrin,SnPP)干预。肺泡灌洗液细胞计数和肺脏病理组织学检测评价哮喘动物模型;real-time PCR和Western blot方法分别测定脾脏细胞内HO-1、IL-10mRNA表达和HO-1蛋白量;ELISA方法测定动物血清OVA-特异性IgE(OVA-sIgE)和IL-10水平;流式细胞计数测定脾脏细胞中CD4+CD25+IL-10+Treg、CD4+IL-10R+IFN-γR+Tr1的比例。结果哮喘小鼠模型经hemin干预后,Tr1数量增加,脾脏细胞内HO-1和IL-10mRNA表达上调,HO-1蛋白水平明显增加,血清IL-10水平增高,哮喘气道炎症减轻。结论在哮喘动物模型中HO-1可能通过诱导Tr1细胞,增加IL-10的分泌,抑制哮喘气道炎症。更多还原

【Abstract】 Objectives To explore the immunosuppressive function of type 1 T regulatory (Tr1) cells after treated with heme oxygenase-1 (HO-1) in asthmatic mouse model. Methods C57B6 mouse was sensitized and challenged by ovalbumin (OVA) and administrated with hemin or Sn-protoporphyrin (SnPP). Airway inflammation was analyzed by cell counting of bronchoalveolar lavage fluid (BALF) and lung histopathology. The expression levels of HO-1, IL-10 mRNA and protein were detected in splenic cells. The levels of OVA-specific IgE (OVA-sIgE) and IL-10 in serum were measured by ELISA. The ratio of CD4 +CD25 +IL-10 +Treg and CD4 +IL-10R +IFN-γR +Tr1 in splenic cells was measured by flow cytometry. Results The expression levels of HO-1, IL-10 mRNA, and the products of HO-1 in splenic cells were enhanced after treated with hemin. The number of Tr1 and the concentration of serum IL-10 were increased in C57B6 mouse sensitized and challenged by OVA and hemin. Airway inflammatory severity was alleviated. Conclusions The study suggests that HO-1 suppresses asthmatic airway inflammation by enhancing the immunosuppressive function of Tr1 cells and secretion of IL-10 in asthma animal model.更多还原