β_2受体激动剂对哮喘豚鼠糖皮质激素受体功能影响的研究

Experimental studies on the effects of β_2 adrenoceptor agonists on the roles of glucocorticoids in asthmatic management

目的 探索 β2 受体激动剂 (β2 AA)对哮喘豚鼠血淋巴细胞糖皮质激素受体 (GR)功能的影响。方法 采用放射性配基结合分析法测定哮喘豚鼠血淋巴细胞GR的Kd 及Bmax,用凝胶阻滞分析法测定GR与糖皮质类固醇反应片段(GRE)的结合能力。结果 各组淋巴细胞GR的Kd 无明显差异 (P >0 0 5 ) ;沙丁胺醇组淋巴细胞GR的Bmax与对照组比较无明显差异 (P >0 0 5 ) ,沙丁胺醇组GR与GRE结合值〔(1 5± 0 4)RDU〕与对照组〔(8 7± 2 4)RDU〕比较差异有显著性 (P <0 0 1) ,地塞米松组GR与GRE组合值〔(15 9± 3 2 )RDU〕与对照组比较差异有显著性 (P <0 0 1) ,沙丁胺醇加地塞米松组 (7d ,14d)GR与GRE结合值〔(4 9±2 1)RDU ,(2 2± 0 8)RDU〕与对照组比较差异有显著性(P <0 0 1) ,且遂渐下降 ,具有时间依赖性。结论 β2 AA可降低GR与GRE的结合能力 ,削弱糖皮质激素的作用 ,长期应用 β2

AIM To study the effects of β 2 adrenoceptor agonists (β 2AA) on the functions of glucocorticoid receptor(GR) in blood lymphocytes of asthmatic guinea pigs. METHODS Measuring K d(affinity)and B max (maximum binding capacity) of GR by radioligand binding assay of receptors(RBA) and the binding of glucocorticoid receptors(GR) and glucocorticoid response elements(GRE) by electrophoretic mobility shift assay(EMSA) in blood lymphocytes of asthmatic guinea pigs. RESULTS The band density of GR and GRE binding in the salbutamol group〔(1 5±0 4) RDU〕 was lower than that〔(8 7±2 4) RDU〕 in the control( P <0 01), and the band density of GR and GRE binding in the dexamethasone〔(15 9±3 2) RDU〕 was higher than that in control( P <0 01). The band desity of GR and GRE binding in the salbutamol+dexamethasone groups〔7 days,14 days,(4 9±2 1) RDU,(2 2±0 8) RDU〕 was respectively lower than that in the control and decreased gradually in a time dependent manner. CONCLUSION β 2AA might decrease the ability of GR and GRE binding and inhibit the anti inflammatory effects of glucocorticoids. It is not suitable for using β 2AA to control asthma in a long term.