环磷酰胺对SD 大鼠生育力与早期胚胎发育毒性阳性模型的建立

摘要: 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。

Positive Modeling Study on Fertility and Early Embryonic Developmental Toxicity of Cyclophosphamide to SD Rats

Abstract: Objective In fertility and early embryonic developmental toxicity test for SD rat，different doses of cyclophosphamide were given by subcutaneous injection，the right dose level was chosen to set up positive model，and background data for laboratory was accumulated． Method One hundred and seventy-six SD rats in 7 － 8 weeks were taken，which males and females were in half．Randomly divided into vehicle control group ( Veh) ，low cyclophosphamide dose group ( L: 10 mg·kg － 1 ) ，moderate cyclophosphamide dose group ( M: 20 mg·kg － 1 ) and high cyclophosphamide dose group ( H: 40 mg·kg － 1 ) ． There were 44 rats in each group and males and females were in half． Males were dosed once a week from the 28th day before mating until to be killed． Females were dosed once a week from the 14th day before mating，and were dosed at the 0 day after mating． Totally treated three times for females． Males and unsuccessful mating females were killed after mating，and the other females were killed at the 14th day after mating． Collected the male fertility，female sexual cycle，pregnancy rate，mortality for pregnant rats and stillbirth rate in each group． Result Toxicity on fertility and early embryonic development in SD rats were appeared in all the dose groups of Cyclophosphamide，and the toxicity increased along with increasing dose level． Conclusion Subcutaneous injection to SD rats with different doses of cyclophosphamide，the high dose group had obvious effect to fertility and early embryonic developmental toxicity，so the high dose group was chosen as positive model in this study．