环磷酰胺不同给药方式对孕兔胎仔致畸作用的比较  

Comparison of teratogenic effects of different administration methods of cyclophosphamide in rabbit fetuses

作　　者：周莉[1] 姜娟[1] 陈颖[1] 王永[1] 崇立明[1] 骆永伟[1] 王华[1] 孙祖越[1] 

机构地区：[1]上海市计划生育科学研究所药理毒理学研究室,中国生育调节药物毒理检测中心,上海200032

出　　处：《中国新药杂志》2013年第13期1505-1509,1537,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2011ZX09301-005);上海市人才发展基金(2010031);上海市实验动物创新行动计划项目(11140901300;11140901303)

摘　　要：目的:比较环磷酰胺不同给药途径、给药剂量和给药时间对孕兔胎仔的致畸作用,为环磷酰胺作为阳性对照物的使用提供依据。方法:新西兰大耳白家兔妊娠后随机分为溶媒对照组(生理盐水)、环磷酰胺A(18 mg.kg-1.d-1,妊娠d 6～d 20,灌胃)、B(25 mg.kg-1.d-1,妊娠d 10～d 13,皮下注射)和C(15mg.kg-1.d-1,妊娠d6～d18,肌内注射)组。妊娠d28处死孕兔,剖宫取胎仔,观察胎仔外观、内脏和骨骼畸形表现。结果:环磷酰胺各组胎仔生长发育均受到明显影响,但不同的剂量和给药途径出现的畸形比例和种类均有差异。B组畸形比例较高,A组出现的胎仔畸形种类最多,畸形比例适当。结论:胚胎器官形成期开始(妊娠d 6)至妊娠d 20连续每日1次灌胃给予环磷酰胺18 mg.kg-1是其作为阳性对照物的最佳使用条件。Objective： To observe and compare the teratogenic action of cyclophosphamide for pregnant rabbits administered through different routes, dosages and time, thus to provide basis for using cyclophosphamide as a positive control in embryo-fetal developmental toxicity test. Methods： Pregnant New Zealand white rabbits were randomly divided into control group （saline） , cyelophosphamide A group （18 mg. kg-1. d- 1 from gestational days （GD） 6 to 20, ig）, B group （25 mg.kg-1 .d-1 from GD 10 to 13, sc）, and C group （15 mg.kg-1 .d-1 from GD 6 to 18, im）. At termination （GD 28） , the uterine content was removed by caesarean section. Live fetuses were examined for external, visceral, and skeletal malformations and variations. Results： Significant differences existed in rabbit malformation rates and types among different eyclophosphamide groups, and the growth and development of fetuses were significantly influenced by eyclophosphamide. The incidence of rabbit malformation in group B was higher than in other groups. Group A had the largest numbers of fetal malformation types and an appropriate malfor- mation proportion. Conclusion ： 18 rag. kg- 1. d -1 （ig） from GD 6 to 20 is the best administration method for eyclo-phosphamide as a positive control for embryo-fetal developmental toxicity test in rabbits.

关 键 词：环磷酰胺 生殖毒性 孕兔 胚胎 胎仔发育毒性试验 阳性对照 

分 类 号：R992[医药卫生—毒理学]