目的探讨生育力与早期胚胎发育毒性试验中,皮下给予不同剂量的环磷酰胺对SD大鼠的影响,选择合适的剂量建立阳性模型,积累实验室背景数据。方法取7~8周龄健康SD大鼠176只,雌雄各半。按体质量随机分为溶媒对照组(Veh)、环磷酰胺低(L:10 mg·kg-1)、中(M:20 mg·kg-1)、高(H:40 mg·kg-1)剂量组,每组44只,雌性各半。雄鼠于交配前28 d开始给药,每周一次,给药期持续整个交配期直至处死;雌鼠于交配前14 d开始给药,交配前每周1次,交配成功后第0天给药1次,总共给药3次。雄鼠及未交配成功雌鼠于交配结束后处死剖检,雌鼠于受孕后第15 d剖检,统计各剂量组雄鼠生育率;雌鼠性周期、妊娠率;孕鼠死亡率和死胎率。结果环磷酰胺低、中、高各剂量组对SD大鼠生育力与早期胚胎发育均有一定的毒性作用,且随给药剂量增加,毒性作用增强。结论皮下给予SD大鼠不同剂量的环磷酰胺,高剂量组对大鼠生育力与早期胚胎发育的毒性影响较为明显,故选择此剂量作为本实验室的阳性模型。 Objective To investigate the effects of different doses of cyclophosphamide administered subcutaneously on SD rats in fertility and early embryonic developmental toxicity test, select the appropriate dose to establish a positive model and accumulate laboratory background data. Methods Sixty-seven healthy SD rats aged 7-8 weeks were randomly divided into male and female. The mice were randomly divided into vehicle control group (Veh), low cyclophosphamide (L: 10 mg · kg -1), medium (M 20 mg · kg -1) and high ) Dose group, 44 in each group, female half and half. The male rats were dosed 28 days before mating, once a week, and the dosing period lasted until the completion of the mating period. The rats were dosed 14 days before mating, once a week before mating and 0 days after the mating was successful Medicine 1 times, a total of 3 times administered. The males and unaccompanied females were sacrificed at the end of mating. The females were necropsied on the 15th day after conception, and the fertility rate of males was calculated. The females’ sexual cycle, pregnancy rate, mortality and stillbirth rate. Results Low, medium and high doses of cyclophosphamide had some toxic effects on the fertility and early embryonic development of SD rats. With the increase of dose, the toxic effects were enhanced. Conclusion Different doses of cyclophosphamide were given subcutaneously in SD rats. The high dose group had obvious effects on the fertility and early embryo development of rats. Therefore, we chose this dose as the positive model of our laboratory.