环磷酰胺对大鼠胚胎脑及骨骼发育的毒性作用

目的探讨环磷酰胺对大鼠胚胎脑及骨骼发育的毒性作用。方法将受孕大鼠随机分为对照组和给药组(设4个剂量:5、10、15、20mg·kg-1),自动物受孕d8开始,给药组分别给予环磷酰胺,对照组给予等量生理盐水,每日1次,连续给药3d。受孕d20处死孕鼠观察环磷酰胺对胎鼠体表、四肢形态、骨骼和脑形态发育的影响。结果给予环磷酰胺5mg·kg-1组胎鼠体表、四肢形态、骨骼和脑形态未见明显变化;10mg·kg-1体重组胎鼠中脑导水管和左右脑室增宽,大脑半球、腰椎骨、肋骨、肢掌骨发育不全;15mg·kg-1组胎鼠侧脑室扩大、大脑皮质、颞叶、双侧被盖区及结合臂发育不全,枕骨缺如,脑膨出,椎骨裂开,肋骨骨化不全,四肢远端骨未骨化;20mg·kg-1体重组未见成形胚胎。结论环磷酰胺对大鼠胚胎脑及骨骼发育有明显的毒性作用。

Toxic effect of cyclophosphamide on the embryonic cerebral and skeleton development of rats

Aim To study toxic effect of cyclophosphamide on the embryonic cerebral and skeleton development of rats.Methods The pregnant rats were randomly divided into control group and experimental group(5,10,15,20 mg·kg-1 body wt).The experimental group was given cyclophosphamide and control group was given normal saline(sc)d 8~10 after becoming pregnant,and all rats were cut open the belly under anesthesia with ether at d 20 of gestation,the effects of cyclophosphamide on the embryonic body,four limbs form,cerebral and skeleton development of rat were observed.Results The embryos of 5 mg·kg-1 group were normal;the aqueduct of midbrain and left and right lateral ventricle expanded,cerebral hemisphere,lumbar vertebrae,rib,metacarpal bone were hypoplasia of embryos of 10 mg·kg-1 group and the symptoms of 15 mg·kg-1 group were graver than those of 10 mg·kg-1 group;20 mg·kg-1 group did not form embryos.Conclusion Cyclophosphamide has significant toxic effect on the embryonic cerebral and skeleton development of rats.