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目的 探讨哮喘豚鼠发作时气道上皮细胞原癌基因c fos的活化与上皮细胞释放内皮素 1(ET 1)的相关性。方法将豚鼠随机分为哮喘组、地塞米松组和正常对照组。以卵蛋白致敏建立哮喘动物组模型 ;再给予肌注地塞米松 (0 .5mg kg)治疗则为地塞米松组。利用Dotblot与Northernblot及免疫组化染色法 ,研究c fos在气道上皮细胞中的表达 ;利用放射免疫法测定各组支气管 肺泡灌洗液 (BALF)中ET 1的含量。结果正常对照组有低水平的c fos基因表达和ET 1合成。哮喘组豚鼠在激发 30min后 ,气道上皮细胞c fosmRNA表达及Fos蛋白染色阳性颗粒都达到高峰 ,持续 2h左右。同时 ,BALF中ET 1的含量在 30min后也达到高峰 ,持续 2～ 3h。地塞米松组的c fosmRNA及蛋白表达水平均明显低于哮喘组 (P <0 .0 1) ,但高于正常对照组 ;并且该组BALF中ET 1的含量也低于哮喘组 (P <0 .0 1)。结论c fos基因活化与ET 1释放在哮喘豚鼠发病中都具有重要作用 ,两者密切相关。ET 1的释放可能受控于c fos基因的活化
Objective To investigate the correlation between the activation of c-fos in airway epithelial cells and the release of endothelin-1 (ET-1) from epithelial cells in asthmatic guinea pigs. Methods Guinea pigs were randomly divided into asthma group, dexamethasone group and normal control group. The animal model of asthma was established by ovalbumin sensitization. Dexamethasone (0.05 mg) was given to dexamethasone group. The expression of c fos in airway epithelial cells was detected by Dotblot, Northern blot and immunohistochemical staining. The content of ET 1 in bronchoalveolar lavage fluid (BALF) was determined by radioimmunoassay. Results The normal control group had low levels of c fos gene expression and ET 1 synthesis. After being stimulated for 30 minutes in asthmatic guinea pigs, the expression of c fos mRNA and Fos protein positive granules in airway epithelial cells all reached the peak, which lasted for about 2 hours. At the same time, the content of ET 1 in BALF also peaked after 30 min for 2 ~ 3 h. The levels of c fos mRNA and protein in dexamethasone group were significantly lower than those in asthma group (P <0.01), but higher than those in normal control group. ET1 level in BALF was also lower in dexamethasone group than in asthma group (P < 0 .0 1). Conclusion Activation of c fos gene and release of ET 1 play an important role in the pathogenesis of asthmatic guinea pigs, and they are closely related to each other. ET 1 release may be controlled by the c fos gene activation