Abstract: Objective To explore the method of establishing rabbit teratogenicity experimental model by oral gavage of cyclophosphamide in the developmental toxicity test of embryo-fetal rabbits, and to provide laboratory background data for the experimental study of teratogenicity. Method Sixty-six healthy pregnant ordinary New Zealand rabbits were selected and divided into lysozyme control group ( 0. 5% sodium carboxymethyl cellulose) and cyclophosphamide poisoning group (20 mg / kg) by random number method according to the weight of objects. After successful mating, pregnant rabbits were given 2 mL / kg intragastrically infected on GD6 - GD18. During the poisoning period, the clinical manifestations were observed, body weight, successful conception rate, luteal number, number of live births, number of stillbirths and number of absorbed fetuses of pregnant rabbits were counted, and body weight, length, appearance deformity, visceral deformity and skeletal deformity of the fetuses were recorded. Result There was no significant difference in body weight between cyclophosphamide group and lysozyme control group(P > 0. 05 ) . The number of luteal body, number of live births and number of implantation of pregnant rabbits in cyclophosphamide group were decreased compared with lysozyme control group, and the differences were statistically significant(P<0. 05) . Fetal weight, body length and placental weight in cyclophosphamide group were all decreased compared with lysozyme control group, and the differences were statistically significant ( P < 0. 05 ) . The appearance, visceral and skeletal abnormalities were significantly increased in the cyclophosphamide group compared with the lysozyme control group, and the difference was statistically significant(P<0. 01, P<0. 05) . Conclusion Cyclophosphamide was poisoned by oral gavage at the dose of 20 mg / kg has a short administration period, a high rate of fetal deformities, a wide variety of deformities, and no maternal toxicity. Therefore, a better positive model of embryo-fetal developmental toxicity can be established.

Key words: cyclophosphamide, rabbit, development toxicity;embryo-fetal

摘要： 目的 探讨兔胚胎-胎仔发育毒性实验中,经口灌胃环磷酰胺建立兔致畸实验模型的方法,为致畸实验研究提供实验室背景数据。 方法 取健康受孕的普通级新西兰兔 66 只,按动物体质量采用随机数字法分为溶酶对照组(0. 5%羧甲基纤维素钠)和环磷酰胺染毒组( 20 mg / kg) ,交配成功后于孕兔 GD6 ~ GD18 按 2 mL / kg 进行灌胃染毒。 染毒期间观察临床表现,统计孕兔的体质量、成功受孕率、黄体数、活胎数、死胎数和吸收胎数等指标,记录胎仔的体质量、身长、外观畸形、内脏畸形和骨骼畸形等指标。 结果 环磷酰胺组孕兔的体质量和溶酶对照组相比,差异无统计学意义(P>0. 05) ;环磷酰胺组孕兔黄体数、活胎数和着床数与溶酶对照组相比均降低,差异均有统计学意义(P<0. 05) ;环磷酰胺组胎仔的重量、身长和胎盘重量与溶酶对照组相比均降低,差异均有统计学意义( P<0. 05) ;环磷酰胺组胎仔的外观、内脏和骨骼的异常发生率明显升高,与溶酶对照组相比,差异有统计学意义( P<0. 01 或 P<0. 05) 。 结论 环磷酰胺经口灌胃染毒,在 20 mg / kg 的灌胃剂量下,给药周期短,胎仔的畸形率高,畸形种类多,不引起母体毒性,可建立较好的兔胚胎-胎仔发育毒性实验模型。

关键词: 环磷酰胺, 兔, 发育毒性, 胚胎-胎仔