哮喘豚鼠气道上皮细胞原癌基因c-fos活化与ET-1释放相关性的研究

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Dot blot与Northern blot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-fos mRNA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-fos mRNA及蛋白表达水平均明显低于哮喘组（P＜0．01），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＜0．01）。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。

Study on correlation between c-fos expression and synthesis and release of endothelin-1(ET-1) in airway epithelial cell in asthmatic guinea-pigs

Aim To investigate the correlation between c-fos expression and release of endothelin-1(ET-1) in epithelial cells of airway in asthmatic guinea-pigs. Methods Guinea-pigs were divided at randomly into asthma group, dexamethasone group and control group. Animals in asthma and dexamethasone group were induced by ovalbumin with or without dexamethasone treatment. Dot blot, Northern blot and immunohistochemical techniques were used to detect the expression of c-fos in airway epitheliums. ET-1 content in bronchoalveolar lavage fluide (BALF) was also assayed by radioimmunoassay. Results There were low c-fos expression and ET-1 content in control group. But c-fos mRNA expression was enhanced significantly in asthma group compared with control (P<0.01), and reached its peak value at 30 min after the onset of asthma. In the meantime, ET-1 content was increased in asthma group as c-fos did. Dexamethasone could inhibit c-fos expression and ET-1 release markedly in epitheliums of asthmatic animals (P<0.01). Conclusion It can be demonstrated that both proto-oncogene c-fos expression and release of ET-1 are important event in the attack of asthma, and they are closely related with each other.