糖皮质激素对哮喘大鼠Clara细胞分泌蛋白表达的影响

目的　观察吸入糖皮质激素对大鼠支气管哮喘 (简称哮喘 )模型肺组织Clara细胞分泌蛋白 (CCSP)mRNA表达的影响。方法　用卵白蛋白 (OVA)致敏、雾化建立大鼠哮喘模型 ,以逆转录 聚合酶链反应 (RT PCR)、斑点免疫印迹法 ,分别检测大鼠激发哮喘 3天后肺组织CCSPmRNA表达水平、支气管肺泡灌洗液 (BALF)CCSP蛋白浓度及雾化吸入布地奈德的影响。结果　哮喘组大鼠肺组织CCSPmRNA表达量为 0 .5 6± 0 .0 5 ,与正常对照组 (0 .6 5± 0 .0 4 )比较差异有显著性 (P <0 .0 1) ;激素治疗组CCSPmRNA表达量为 0 .6 3± 0 .0 4 ,与哮喘组 (0 .5 6± 0 .0 5 )比较差异也有显著性 (P <0 .0 5 )。哮喘组大鼠BALF中CCSP蛋白含量为 4 9± 5 ,与正常对照组 (6 0± 5 )比较 ,差异有显著性 (P <0 .0 1) ;激素治疗组CCSP蛋白含量 (5 7± 5 )与哮喘组比较 (P <0 .0 5 ) ,BALF中嗜酸细胞比例降低 ,气道炎症反应减轻。结论　CCSPmRNA表达减少导致CCSP水平下降 ,从而促进气道炎症而参与哮喘发病。雾化吸入糖皮质激素可增加CCSPmRNA表达 ,抑制哮喘气道炎症。

Effect of budesonide on Clara cell secretory protein and its mRNA expression in a rat model of asthma

OBJECTIVE: To investigate the effect of inhaled glucocorticoids on the expression of Clara cell secretory protein (CCSP) and its mRNA in lung tissue of a rat model of asthma. METHODS: The rat asthmatic model was established by sensitizing and challenging SD rats with aerosolized ovalbumin (OVA). Rats were divided into a control, an asthmatic and a glucocorticoid groups. Budesonide aerosol was delivered by a jet nebulizer. The CCSP mRNA level in the lung tissue and the CCSP level in bronchoalveolar lavage fluid (BALF) were determined by RT-PCR and dot immuno-blotting, respectively. RESULTS: The level of CCSP mRNA in the lung tissue was 0.65 +/- 0.04 in the control, 0.56 +/- 0.05 in the asthmatic and 0.63 +/- 0.04 in the glucocorticoid groups, respectively (asthma versus control, P < 0.01; glucocorticoid versus asthma, P < 0.05). The CCSP level in BALF was 60 +/- 5 in the control, 49 +/- 5 in the asthmatic and 57 +/- 5 in the glucocorticoid groups, respectively (asthma versus control, P < 0.01; glucocorticoid versus asthma, P < 0.05). Budesonide reduced the percentage of eosinophils in BALF and inhibited airway inflammation. CONCLUSIONS: OVA challenge in the rat model decreased CCSP mRNA, resulting in a reduction in CCSP production, which may contribute to asthmatic airway inflammation. Inhaled glucocorticoids increased the expression of CCSP mRNA in lung tissue, which may be a mechanism for the suppression of airway inflammation by glucocorticoids.