兔胚胎-胎仔发育毒性试验中环磷酰胺给药方式的探讨

发布时间：2018-01-14 01:05

本文关键词：兔胚胎-胎仔发育毒性试验中环磷酰胺给药方式的探讨　出处：《中国比较医学杂志》2017年07期 　论文类型：期刊论文

【摘要】：目的探讨环磷酰胺不同给药途径、给药剂量对妊娠家兔胚胎及胎仔的影响,以确定诱导胎兔畸形最佳的给药方式。方法孕兔分为生理盐水对照C组、静脉注射Y1组(15 mg/kg)、皮下注射低剂量Y2组(20 mg/kg)和皮下注射高剂量Y3组(30 mg/kg),各组均在GD10~13(受孕当天为GD0)分别按相应途径给药。GD28解剖,检查黄体数、着床数、连胎子宫重、吸收胎率;取胎仔,检查胎仔性别、身长、尾长、活胎数、死胎数,并按要求进行外观畸形、内脏畸形和骨骼畸形的检查。结果环磷酰胺静脉注射组及皮下注射低剂量组孕兔胎仔均出现了畸形,两组外观畸形率分别为30.77%和95.65%,骨骼畸形率分别为7.69%和73.91%,内脏畸形率分别为20.51%和47.83%。皮下注射高剂量组吸收胎发生率为100%。结论孕兔在GD10~13皮下注射环磷酰胺20 mg/kg可用作家兔胚胎-胎仔毒性发育试验的阳性给药方法。该方法给药周期短,操作方便,吸收胎少,胎仔畸形率高,可为同行选择合适的兔胚胎-胎仔发育毒性阳性模型提供依据。
[Abstract]:Objective to investigate the effects of different administration routes of cyclophosphamide on embryo and fetus of pregnant rabbits and determine the best way to induce fetal malformation. Methods pregnant rabbits were divided into normal saline control group C. 15 mg / kg of Y1 group, 20 mg / kg of Y2 group (subcutaneously) and 30 mg / kg of high dose Y3 group (subcutaneously). All groups were treated with GD10 ~ (13) (GD0 on the day of pregnancy) according to the corresponding route. The number of corpus luteum, the number of implantation, the weight of uterus and the rate of absorption of fetus were examined. Take the fetus, check the fetus sex, length, tail length, number of live births, number of stillbirths, and according to the requirements for appearance deformities. Results there were deformities in fetus of pregnant rabbits in cyclophosphamide intravenous injection group and subcutaneous injection low dose group. The appearance deformity rates of the two groups were 30.77% and 95.65% respectively. The skeletal deformities were 7.69% and 73.91% respectively. The rates of visceral malformation were 20.51% and 47.83, respectively. The incidence of fetal resorption in the high dose group was 100. Conclusion the pregnant rabbits were injected with cyclophosphamide 20 subcutaneously in GD10~13. Mg/kg can be used as a positive administration method for embryo-fetal toxicity development test in rabbits, which has a short period of administration. It is easy to operate, absorb fewer fetuses, and have high fetal malformation rate, which can provide the basis for selecting suitable positive model for the development toxicity of rabbit embryos and foetus.
【作者单位】：湖北省医药工业研究院有限公司/湖北省药物安全性评价中心;
【分类号】：R-332;R965
【正文快照】： 生殖毒性研究是药物非临床研究的重要内容,是药物进入临床研究及上市的重要环节。生殖Ⅱ段,即胚胎-胎仔发育毒性试验,研究胚胎从着床到硬腭闭合期间给药,受试药物是否具有胚胎毒性或致畸性。胚胎-胎仔发育毒性试验需选用两种哺乳动物,一般非啮齿类选择家兔[1]。国内外关于家兔

【相似文献】