醋酸棉酚与米索前列醇对大鼠和小鼠的抗早孕研究

用抗早孕实验和大鼠子宫离体实验,研究了醋酸棉酚与米索前列醇抗早孕的协同作用。结果表明,早孕小鼠单服米索,其终止早孕作用微弱;当与棉酚合用时,对小鼠的抗早孕作用增强。对离体大鼠子宫,米索有明显的增强宫缩作用,而棉酚则无影响,但早孕大鼠po棉酚80mg·kg^-1·d^-1,3d后其子宫对米索的敏感性较对照组有显著提高。大鼠于妊娠d 6～8 po棉酚或米索,或两药剂量的一半合并用药,可使子宫蜕膜组织损伤,而以两药合用组最为严重,但子宫孕酮受体含量和分布与对照组相似。结果提示,两药合用有协同抗早孕作用。

EFFECT OF GOSSYPOL IN COMBINATION WITH MISOPROSTOL ON TERMINATION OF EARLY PREGNANCY IN RATS AND MICE

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.