抗孕唑配伍米非司酮提高止孕活性的机理(英文)  

Synergistic effects on pregnancy-termination activity of DLlll-IT in combination with mifepristone

作　　者：杨波[1] 方瑞英[1] 

机构地区：[1]浙江医科大学药学系药理教研室,杭州,310031,中国

出　　处：《中国药理学报》1996年第4期361-362,共2页Acta Pharmacologica Sinica

基　　金：Project supported by the National Natural Science Foundation of China,№ 3947082.

摘　　要：目的:研究抗孕唑(DL111-IT)与米非司酮(Mif)合用抗早孕的作用点。方法:用组织学和细胞培养法观察对细胞的损伤;放射配基分析及PAP免疫组化观察子宫胞浆孕酮受体(PR)的影响。结果:两药合用,单用均造成蜕膜细胞坏死,胚胎生长抑制,以合用药组损伤力最强;药物作用于人蜕膜细胞24h的LD_(50)(mg·L^(-1))为:dL111-IT 18.1(15.1—21.4),Mif25.0(23.1—26.9),合用DL111-IT5.0+Mif3.5(1.8—6.5)。im DL111-IT24h及48h的PR与对照组比,含量下降47％,与Mif的结合率不变。结论:DL111-IT使PR数量下降,不影响Mif与PR的结合率,少量Mif即可有效拮抗孕酮;DL111-IT增强Mif对蜕膜细胞的损伤作用,影响胚胎发育而终止早孕。AIM: TO clarify the role of DL111-IT when combined with mifepristone (Mif) on termination of early pregnancy. METHODS: Progesterone receptors (PR) was measured using radioligand assay ( RA ), and peroxidase-antiperoxidase ( PAP ) immuno-histochemistry. Decidual cells (DC) were estimated using cell culture and histological examination (HE) (including fetus). RESULTS: DL111-1T 100 mg · kg-1 im, Mif 5 mg·kg-1 ig, DL111-IT 16 mg·kg-1 im ± Mif 1.5 mg·kg-1 ig and tea seed oil (TSO) 2 mL·kg-1 im on d 7 of pregnancy in rats, DC and fetus of treated groups were found to be degenerated at 24 h after treatment, at 48 h after treatment, PAP labeling index (%) of uterus PR of 4 groups were 22 ± 4, 18.7 ± 2.9, 10.3 ±1.2, 52 ± 15, respectively. Rats im DL111-IT 100 mg·kg-1 24 h after treatment, the quantity of PR decreased by 47 % vs that of ISO. The affinity of PR with Mif and progesterone did not change. Cultured human DC were exposed to DL111-IT and Mif 0 -50 mg·L-1, alone or combinatively, for 24 h. LD50(mg·L-1) were: DL111-IT 18.1 (15.1-21.4), Mif 25.0 (23.1 - 26.9), DL111-IT5.0 plus Mif 3.5 (1.8-6.5) or Mif 5.0 plus DL111-IT 4.6 (1.1-7.3), respectively. CONCLUSION: DL111-IT enhanced action of Mif on DC, reduced quantity of PR, so the 2 drugs had the synergistic action in termination of early pregnancy.

关 键 词：米非司酮 抗孕唑 蜕膜 黄体酮 受体 胎儿 

分 类 号：R979.22[医药卫生—药品] R969.4[医药卫生—药学]