胚胎－ 胎仔发育毒性试验中阳性模型的建立

摘要: 目的探讨SD 大鼠胚胎－ 胎仔发育毒性试验中，皮下给予不同剂量的环磷酰胺进行其剂量相关性的比较研究，建立阳性模型，积累实验室背景数据。方法取健康受孕SD 大鼠100 只，按体质量随机分为溶媒对照组( Veh:7. 5 mg·kg － 1 氯化钠注射液) 、环磷酰胺低( L: 7 mg·kg － 1 ) 、中( M: 10 mg·kg － 1 ) 、高( H: 15 mg·kg － 1 ) 剂量组，每孕鼠组不少于20 只，按程序皮下注射给药，观察临床表现，统计各剂量组孕鼠的体质量、摄食量、窝质量、黄体数、着床数、活胎数、死胎数和吸收胎数等指标，以及胎鼠的性别、体质量、身长、外观畸形、内脏畸形和骨骼畸形等指标。结果环磷酰胺低、中、高各剂量组对大鼠胚胎－ 胎仔发育均有毒性作用且具有明显的量效关系。结论皮下给予不同剂量的环磷酰胺对大鼠胚胎－ 胎仔发育毒性均产生影响且具有明显的量效关系，三种给药剂量均可建立胚胎－ 胎仔发育毒性试验阳性模型。

Establishment of Positive Model for Embryo-fetal Developmental Toxicity Test

Abstract: Objective In embryo － fetal developmental toxicity test for SD rat，different doses of cyclophosphamide were given by subcutaneous injection to study the comparison of relativity between dose levels and clinical manifestation，establish a positive model and accumulate background data for laboratory． Method One hundred healthy pregnant SD rats were taken，randomly divided into solvent control group ( 7． 5 mg·kg － 1 Veh: sodium chloride injection) ，low cyclophosphamide dose group ( L: 7 mg·kg － 1 ) ，moderate cyclophosphamide dose group ( M: 10 mg·kg － 1 ) and high cyclophosphamide dose group ( H: 15 mg·kg － 1 ) ． There was not less than 20 pregnant rats in each group． Subcutaneous injection was required and clinical manifestation was observed． Collected the body weight，food intake，litter weight，corpus luteum number，implantation number，the number of live births，the number of stillborn fetus and the number of absorptive fetus of pregnant rats in each group，and the sex ratio，body weight，body length，appearance abnormality，visceral abnormality and skeletal abnormality of fetal rats were also observed． Ｒesult Developmental toxicity were observed in all cyclophosphamide dose groups and dose － effect relationship was found obviously． Conclusion Developmental toxicity and obvious dose － effect relationship were observed in all cyclophosphamide dose groups by subcutaneous injection． A positive model of embryo － fetal developmental toxicity test can be set up by all three dose levels of cyclophosphamide．