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探讨血红素加氧酶-1(HO-1,hemeoxygenase-1)介导CD4+CD25High调节性T淋巴细胞(Treg,regulatoryTcells)拮抗哮喘气道炎症的作用.用卵清蛋白(OVA)致敏、激发小鼠制备并建立哮喘动物模型,并在致敏、激发过程中经氯化高铁血红素(Hemin)或锡-原卟啉(SnPP,Sn-protoporphyrin)处理.分别测定激发后各组动物血清OVA特异性IgE,支气管肺泡灌洗液中(BALF,bronchialalveolarlavagefluid)细胞总数和嗜酸性粒细胞(EOS,eosinophil)数及外周血CD4+CD25HighTreg细胞变化和肺组织HO-1和Foxp3mRNA表达量,结合病理切片分析气道炎症状况.结果显示:OVA组、Hemin组、SnPP组血清OVA-特异性IgE和BALF中细胞总数及EOS数明显高于正常对照组,但Hemin组IgE水平及BALF中细胞总数和EOS数明显低于OVA组;而OVA组和SnPP组间IgE水平及BALF中细胞总数和EOS数无显著性差异;病理组织学显示OVA组、Hemin组和SnPP组气道组织均见EOS浸润,但Hemin组气道炎症仍明显轻于OVA组和SnPP组;Hemin组外周血CD4+CD25HighTreg细胞比例及肺组织Foxp3mRNA相对表达量明显高于OVA组.Hemin显著上调HO-1表达.实验表明,用Hemin诱导HO-1高表达后外周血CD4+CD25HighTreg细胞比例及Foxp3mRNA相对表达量明显升高,同时血清OVA特异性IgE明显下降,BALF中细胞总数和EOS数减少,气道炎症减轻;提示HO-1可通过提高CD4+CD25HighTreg细胞比例并增强其功能来调节体内Th1/Th2平衡,在支气管哮喘中起到保护作用.
To investigate the effect of hemeoxygenase-1 (HO-1) mediated CD4 + CD25High regulatory T cells on airway inflammation in asthmatic mice.With ovalbumin (OVA) sensitization, The mice were induced to establish asthmatic models and were sensitized and challenged with Hemin or SnPP (Sn-Protoporphyrin) .The serum levels of each group of animals OVA-specific IgE, total number of bronchoalveolar lavage fluid (BALF), eosinophil and CD4 + CD25High Treg cells in peripheral blood and expression of HO-1 and Foxp3mRNA in lung tissue, The results showed that the total number of OVA-specific IgE and BALF and the number of EOS in OVA, Hemin and SnPP groups were significantly higher than those in normal control group, but IgE levels in Hemin group, total number of cells in BALF and The number of EOS in OVA group and SnPP group was significantly lower than that in OVA group. The level of IgE in OVA group and SnPP group was not significantly different from the total number of EOS and BALF cells. Histopathology showed that EOS infiltration was found in OVA, Hemin and SnPP airways, But Hemin group airway inflammation is still obvious In OVA and SnPP groups, the proportion of CD4 + CD25High Treg cells in peripheral blood and the relative expression of Foxp3mRNA in lung tissue were significantly higher in Hemin group than in OVA group.Hemin up-regulated the expression of HO-1.The results showed that peripheral blood level of HO-1 The proportion of CD4 + CD25High Treg cells and the relative expression of Foxp3 mRNA were significantly increased, meanwhile serum OVA-specific IgE was significantly decreased, while the total number of cells and EOS in BALF was decreased and the airway inflammation was relieved; suggesting that HO-1 could increase the proportion of CD4 + CD25High Treg cells And enhance its function to regulate Th1 / Th2 balance in the body, which plays a protective role in bronchial asthma.