β_2受体激动剂影响糖皮质激素治疗支气管哮喘作用的实验研究

An Experimental Study of the Effects of 2-Adrenoceptor Agonists on the Role of Glucocorticoid Receptro in Asthmatic Guinea Pigs

目的 通过研究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 ,探讨β2 AA影响糖皮质激素治疗支气管哮喘的作用。方法 5 0只豚鼠 ,随机分为对照组 (10只 ) ,沙丁胺醇组 (10只 ) ,地塞米松组 (10只 ) ,地塞米松加沙丁胺醇组 (2 0只 )。采用放射性配基结合分析法测定哮喘豚鼠血淋巴细胞 GR的亲和力 (kd)及受体最大结合容量 (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 沙丁胺醇组 GR与 GRE结合值与对照组比较有极明显升高 (p<0 .0 1) ,地塞米松组 GR与 GRE结合值与对照组比较也极明显升高 (p<0 .0 1) ,沙丁胺醇加地塞米松组 (7日 ,14日 ) GR与 GRE结合值与对照组比较则极明显下降 (p<0 .0 1) ,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

Objective To study the effects of (2 adrenoceptor agonists ((2AA) on the functions of glucocorticoid receptor (GR) in blood lymphocytes of asthmatic guinea pigs.Methods Fifty asthmatic guinea pigs were randomly divided into three groups: the control group (n=10), the salbutamol group (n=10) and the salbutamol+dexamethasone group (n=20). The data were collected by measuring Kd (affinity) and Bmax (maximum binding capacity) of GR by radioligand binding assay of receptors (RBA) and the binding of glucocorticoid receptors (GR) and glucorcorticoid 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 was significantly lower than that in the controls ( p < 0.01) and the band density of GR and GRE binding in the dexamethasone group was significantly higher than that in the controls (p <0 .01). The band density of GR and GRE binding in the salbutamol+dexamethasone group (7 days; 14 days) was respectively significantly lower tan that in the controls and decreased gradually in a time dependent manner.Conclusion β 2 AA might decrease the ability of GR and GRE binding and inhibit the anti inflammatory effects of glucocorticoids. The long term use of β 2 AA to control asthma is not advisable.