抗孕唑啉对啮齿类动物终止妊娠药效学研究

Pharmacodynamics of Contragestazolin (L14105) on Pregnancy Termination in Rodents.

目的:研究抗孕唑啉(L14105)的终止妊娠作用及其作用靶部位。方法:用多种啮齿类动物观察终止早孕及中孕作用;用组织学和细胞培养法观察对细胞的损伤;放射配基分析对子宫胞浆孕酮受体的结合力。结果:L14105对小鼠、大鼠、金黄地鼠与豚鼠均有较强的抗早孕作用,并可致豚鼠中孕堕胎;对体外培养人蜕膜细胞具杀伤力,早孕大鼠用药后24～48h蜕膜细胞开始损伤、胚胎吸收;对大鼠子宫胞浆孕酮受体结合力微弱。结论:L14105对多种啮齿类动物具有很强的终止早孕与中孕活性,其作用靶部位可能为蜕膜细胞。

Objective:To study the effect of L14105 on pregnancy termination in rodents and its target site. Method: pregnancy terminating activities were investigated by some species of rodents; Affinity to progesterone receptors was measured using radioiigand binding assay. Decidual cells were estimated using cell culture and histological examination. Result: After par-enteral or oral administration of L14105 showed a potentially early and mid pregnancy - terminating activity in mice, rats., hamsters and guinea pigs. L14105 had low affinity to rat uterus progesterone receptor. When cultured human decidual cells were exposed to L14105 0.077 and 0.155mmol/L for 24-48h, the cells viability markedly dropped in comparison with vehicle control. Histological examination of conceptuses of ratsshowed edema, degeneration, necrosis and nuclei shrik-able or disappear ance of the decidual cells and embryos absorbable after the sc administration of 5mg/kg of L14105 for 24-48h. Conclusion: L14105 showed a potentially pregnancy- terminating activity in rodents. Its target site of contragestional action is probably decidual cells.