Chen Y, Cao L, Gu Z P
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031.
Yao Xue Xue Bao. 1997 Nov;32(11):801-7.
Treatment of mice with misoprostol alone at doses ranging from 200 to 6400 micrograms.kg-1, qid on day 6-8 or bid on day 9 of gestation, the rate of effective early pregnancy interruption were low and showed no dose effect relation. When giving misoprostol 200-6400 micrograms.kg-1 bid on day 9 of gestation following administration of gossypol 50 mg.kg-1 qid on day 6-8, the rate of abortion increased as the dose of misoprostol increased, and the ED50 of misoprostol was 397.8 micrograms.kg-1. The ED50 of gossypol given orally on day 6-8 of gestation was 69.4 mg.kg-1. However, when gosyypol was given in combination with misoprostol 400, 800 or 1600 micrograms.kg-1 on day 9 bid, the ED50 of gossypol decreased to 63.2, 48.6 or 34.9 mg.kg-1, respectively. The results suggest that combination of gossypol and misoprostol showed synergistic effect on termination of early pregnancy in mice. Misoprostol obviously strengthened the uterine contraction of rats both in early pregnancy and estrus in vitro. The contraceptive intensity of contraction was increased as the dose of misoprostol increased from 10(-9), 10(-8) to 10(-7) mol.L-1, and the estrus group was higher than the early pregnancy group (P < 0.01). Gossypol(10(-5)-10(-6) mol.L-1) showed no effect on the uterine activity in rats, but the sensitivity of the uterus of the early pregnant rats to misoprosrol was found to be significantly increased by treatment with gossypol on day 6-8 of gestation (P < 0.01). Degeneration of the decidual was observed under light microscopy when gossypol 80 mg.kg-1.d-1, or misoprostol 800 micrograms.kg-1.d-1, or gossypol 40 mg.kg-1.d-1 combined with misoprostol 400 micrograms.kg-1.d-1 was given orally to rats on day 6-8 of pregnancy. The degeneration of cells was more remarkable when both drugs were given in combination. The assay of immunoreactivity for PR demonstrated that the distribution and content of PR in uterine decidua had no difference between the control group and the treated groups.
在妊娠第6 - 8天，每天4次给予小鼠剂量范围为200至6400微克/千克的米索前列醇，或在妊娠第9天每天2次给药，早期妊娠中断的有效率较低，且未显示出剂量效应关系。在妊娠第6 - 8天每天4次给予棉酚50毫克/千克后，于妊娠第9天每天2次给予200 - 6400微克/千克的米索前列醇，流产率随米索前列醇剂量增加而升高，米索前列醇的半数有效剂量（ED50）为397.8微克/千克。妊娠第6 - 8天口服棉酚的ED50为69.4毫克/千克。然而，当棉酚与米索前列醇400、800或1600微克/千克在第9天联合给药时，棉酚的ED50分别降至63.2、48.6或34.9毫克/千克。结果表明棉酚与米索前列醇联合应用对小鼠早期妊娠终止有协同作用。米索前列醇在体外明显增强了大鼠妊娠早期和发情期的子宫收缩。随着米索前列醇剂量从10^(-9)、10^(-8)增加到10^(-7)摩尔/升，收缩的避孕强度增加，发情期组高于妊娠早期组（P < 0.01）。棉酚（10^(-5) - 10^(-6)摩尔/升）对大鼠子宫活动无影响，但在妊娠第6 - 8天用棉酚处理后，发现妊娠早期大鼠子宫对米索前列醇的敏感性显著增加（P < 0.01）。在妊娠第6 - 8天给大鼠口服棉酚80毫克/千克·天，或米索前列醇800微克/千克·天，或棉酚40毫克/千克·天与米索前列醇400微克/千克·天联合给药时，在光学显微镜下观察到蜕膜变性。两种药物联合给药时细胞变性更明显。孕激素受体（PR）免疫反应性检测表明，对照组和治疗组子宫蜕膜中PR的分布和含量无差异。
