摘要
目的 :探讨米非司酮与糖皮质激素受体的相互作用关系及抗糖皮质激素作用。方法 :以3 H 地塞米松(3 H DEX)作为示踪物 ,采饱和竞争抑制分析法测定米非司酮与大鼠肝胞浆糖皮质激素受体的相对结合亲和力 ;以培养的大鼠胸腺细胞作为模型 ,采3 H 胸腺嘧啶脱氧核苷 (3 H TdR)掺入法 ,研究米非司酮糖皮质激素和抗糖皮质激素活性。结果 :米非司酮可与大鼠肝脏糖皮质激素受体结合 ,较低浓度范围内就可抑制地塞米松与糖皮质激素受体结合 ,与地塞米松相比较 ,米非司酮的相对结合亲和力 (RBA)为 (344 .4 1± 5 7.4 1,5 0 ) %抑制浓度 (IC50 )为 (4.2 1± 1.0 2 )nmol·L-1。在很低浓度时地塞米松就可明显抑制3 H TdR掺入培养的胸腺细胞DNA ,而米非司酮对3 H TdR掺入无明显影响 ,但在高浓度时对3 H TdR掺入有一定的抑制作用。同时米非司酮能拮抗地塞米松诱导的3 H TdR掺入抑制作用。结论 :米非司酮具有一定的糖皮质激素作用和抗糖皮质激素作用 ,但其糖皮质激素样作用比较弱。
Objective: To analyze the glucocorticoid and anti-gluco-corticoid activities of Mifepristone. Methods: With radioligand binding assay, the receptor binding affinity of Mifepristone to the rat liver glucocorticoid receptor and the effect of Mifepristone on 3 H-thymidine incorporation into cutured rat thymocytes were measured. Results: Compared with that of dexamethasone, the relative binding affinity of Mifepristone was (344.41±57.41), and the 50% inhibitory concentration was (4.21±1.02)nmol·L -1 . Dexamethasone could significantly inhibit the 3 H-thymidine incorporation into cellular DNA at a very low concentration. Generally, Mifepristone could not affect 3 H-thymidine incorporation at the same concentration, but at a higher concentration, the Mifepristone had slight glucocorticoid activity. Also Mifepristone could antagonize the inhibitory effect of 3 H-thymidine incorporation induced by dexamethasone. Conclusion: Mifepristone, as a strong agent of antiprogestin, can block progesterone and glucocorticoid activities, and the anti-glucocorticoid effect of Mifepristone should be payed enough attention in the clinical use of this drug.
出处
《武汉大学学报（医学版）》
CAS
2005年第1期93-95,99,共4页
Medical Journal of Wuhan University
