摘要
目的观察环磷酰胺1次染毒或连续染毒对大鼠致畸敏感期的毒性反应。方法选用SD大鼠,设对照组(生理氯化钠)、7.0、15.0mg/kg染毒组,每组6只孕鼠。15.0mg/kg组于孕第12天1次皮下注射染毒;7mg/kg组于孕第11～13天连续皮下注射染毒3次。观察孕鼠体质量及一般健康状况,于妊娠第20天解剖并记录子宫连仔鼠质量、胎盘质量、仔鼠体质量、黄体数、死仔和活仔鼠数、仔鼠身长和尾长;检查仔鼠外观、骨骼和内脏。结果①2个染毒组的孕鼠染毒后均很快出现毒性反应,精神状态明显变差、活动减少、体质量减轻;②7.0和15.0mg/kg染毒组死仔率分别为60.29%和18.37%,明显高于对照组的1.69%(P<0.05);子宫连仔质量、胎盘质量、鼠仔体质量、身长、尾长均明显低于对照组(P<0.05);③染毒组存活仔鼠普遍发生脑膜膨出,骨骼骨化不全,15.0mg/kg组仔鼠大多数出现并趾、少趾、足外翻、短肋、缺肋等异常。结论大鼠致畸敏感期1次(15.0mg/kg)或连续3次(7.0mg/kg)皮下注射环磷酰胺,均可导致明显的胚胎毒性反应,毒性反应的严重程度与染毒时间和剂量密切相关。
Objective To examine the toxicity of a teratogenic agent cyclophospharmide （CP） in the sensitive period of pregnant SD rats after a single or multiple subcutaneous injections.Methods 18 pregnant SD rats were divided into control group （normal saline）,15.0 mg/kg group （CP） and 7.0 mg/kg group （CP） randomly （6 pregnant rats per group）.Rats at 15.0 mg/kg group were administrated with a single subcutaneous injection of CP on the 12th day of gestation.Rats in 7.0 mg/kg group were administrated with 3 times of subcutaneous injection of CP on the 11th,12th and 13th day of gestation.Body weight and general condition were observed during the study.On the 20th day of gestation,all the rats were sacrificed.Respectively examined were the weight of matrix including fetuses,placenta,and fetus,the numbers of corpus luteum,early dead fetus,late dead fetus,and alive fetus,the length of fetal body and tail,and the outward appearance of fetus,fetal skeleton,and fetal viscera.Results Rats administrated with CP appeared cachexia,inactive and weight loss.Fetal death rates at 7.0 and 15.0 mg/kg CP groups were 60.29% and 18.37% respectively,which significantly higher than that in the control group （1.69%,P0.05）.The weight of matrix including fetuses,placenta,and fetus,and the length of fetal body and tail in CP administrated groups were lower than those in the control（P0.05）.Most of the alive fetuses in CP administrated group appeared meningocele and incomplete ossification.In 15.0 mg/kg group,a majority of alive fetuses expressed abnormality including syndactyly,oligodactyly,strephexopodia,short rib and absent rib.Conclusion Single （15.0mg/kg） or 3 consecutive （7 mg/kg） subcutaneous injection of CP could induce embryonic toxicity in sensitive period in pregnant rats and toxic severity was associated with the time and the dose of CP administration.The dose of 7.0 mg/kg of CP can induce more dead fetus and is not suitable for positive control in test of toxicity evaluation.
出处
《中国职业医学》
CAS
北大核心
2010年第3期230-232,共3页
China Occupational Medicine
关键词
环磷酰胺
大鼠
致畸毒性
Cyclophosphamide
Rats
Teratogenicity
