布地奈德对哮喘大鼠模型肺组织血红素氧合酶-1的调控作用

Effect of budesonide on the heme oxygenase-1 expression in lung tissues of rats with asthma

摘要:

目的：研究大鼠哮喘模型肺组织血红素氧合酶-1(heme oxygenase-1，HO-1)蛋白及基因表达特点，以及布地奈德(budesonide，BUD)对HO-1蛋白及基因表达的影响。方法：用卵清蛋白(OVA)致敏、激发大鼠建立哮喘动物模型,并在致敏、激发过程中分别经地塞米松(DXM) 、血晶素(Hemin)及BUD处理。分别测定激发后各组动物全血COHb 的百分比含量；计算肺泡灌洗液（BALF）沉渣中细胞总数和分类百分比；进行支气管周围炎性细胞浸润评分；利用免疫组化和RT-PCR检测方式观察HO-1在哮喘大鼠肺组织的蛋白及基因表达。结果：肺组织的病理改变及BALF细胞学检测显示Hemin (H)组、DXM (D)组和BUD (B)组炎性细胞浸润较哮喘(A)组有显著减轻(P<0.01或P<0.05）。与对照(C)组相比，A、H、D和B组HO-1蛋白、基因表达以及碳氧血红蛋白(COHb)含量显著性升高(P<0.01)；而与A组相比，H、D和B组HO-1蛋白及mRNA表达亦显著升高(P<0.01或P<0.05）；D组和H组COHb含量显著升高（P<0.05）。结论：哮喘大鼠的肺组织HO-1表达水平及活性显著增加，提示HO-1可能参与了哮喘的发病过程；HO-1对大鼠哮喘模型气道炎症有保护作用；BUD和DXM对大鼠哮喘模型气道炎症有保护作用，可能通过上调肺组织HO-1表达实现。

Abstract:

OBJECTIVE: To study the expression of heme oxygenase-1 (HO-1) gene and protein and the effect of budesonide (BUD) on the HO-1 expression in lung tissues in rats with asthma.METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups: normal control, asthma model, dexamethasone (DXM)-, hemin (HO-1 challenger)-or BUD-treated asthma. The asthma model was prepared by ovalbumin sensitization and challenge. The rats were sacrificed 24 hrs after the last challenge. The blood COHb content, and the total cell count and the percentage of differential cells in bronchoalveolar lavage fluid (BALF) were measured. The expression of HO-1 protein and mRNA in lung tissues was detected with immunohistochemistry and RT-PCR, respectively. The airway inflammation situations were evaluated by histopathology.RESULTS: The airway inflammatory cell infiltration in the DXM-, hemin- and BUD-treated asthma groups was remarkably alleviated compared with that in the asthma model group. Compared with the normal control group, the expression of HO-1 mRNA and protein in lung tissues and the blood COHb content in the asthma model and the DXM-, hemin- and BUD-treated asthma groups were significantly up-regulated. The DXM-, hemin- and BUD-treated asthma groups showed significantly increased expression of HO-1 protein and mRNA in lung tissues compared with the asthma model group. The blood COHb content in the DXM-and the hemin-treated asthma groups was significantly higher than that in the asthma model group.CONCLUSIONS: The expression of HO-1 protein and mRNA in lung tissues and blood HO-1 activity increased in rats with asthma, suggesting that HO-1 may be involved in the pathogenesis of asthma. HO-1 may have a protective effect against the airway inflammation in asthmatic rats. BUD and DXM can up-regulate the expression of HO-1 protein and mRNA, thus providing protective effects against the airway inflammation in asthmatic rats.