兔胚胎-胎仔發(fā)育毒性試驗(yàn)中環(huán)磷酰胺給藥方式的探討
本文關(guān)鍵詞:兔胚胎-胎仔發(fā)育毒性試驗(yàn)中環(huán)磷酰胺給藥方式的探討 出處:《中國比較醫(yī)學(xué)雜志》2017年07期 論文類型:期刊論文
更多相關(guān)文章: 胚胎-胎仔發(fā)育 胚胎畸形 環(huán)磷酰胺 兔
【摘要】:目的探討環(huán)磷酰胺不同給藥途徑、給藥劑量對妊娠家兔胚胎及胎仔的影響,以確定誘導(dǎo)胎兔畸形最佳的給藥方式。方法孕兔分為生理鹽水對照C組、靜脈注射Y1組(15 mg/kg)、皮下注射低劑量Y2組(20 mg/kg)和皮下注射高劑量Y3組(30 mg/kg),各組均在GD10~13(受孕當(dāng)天為GD0)分別按相應(yīng)途徑給藥。GD28解剖,檢查黃體數(shù)、著床數(shù)、連胎子宮重、吸收胎率;取胎仔,檢查胎仔性別、身長、尾長、活胎數(shù)、死胎數(shù),并按要求進(jìn)行外觀畸形、內(nèi)臟畸形和骨骼畸形的檢查。結(jié)果環(huán)磷酰胺靜脈注射組及皮下注射低劑量組孕兔胎仔均出現(xiàn)了畸形,兩組外觀畸形率分別為30.77%和95.65%,骨骼畸形率分別為7.69%和73.91%,內(nèi)臟畸形率分別為20.51%和47.83%。皮下注射高劑量組吸收胎發(fā)生率為100%。結(jié)論孕兔在GD10~13皮下注射環(huán)磷酰胺20 mg/kg可用作家兔胚胎-胎仔毒性發(fā)育試驗(yàn)的陽性給藥方法。該方法給藥周期短,操作方便,吸收胎少,胎仔畸形率高,可為同行選擇合適的兔胚胎-胎仔發(fā)育毒性陽性模型提供依據(jù)。
[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.
【作者單位】: 湖北省醫(yī)藥工業(yè)研究院有限公司/湖北省藥物安全性評價(jià)中心;
【分類號(hào)】:R-332;R965
【正文快照】: 生殖毒性研究是藥物非臨床研究的重要內(nèi)容,是藥物進(jìn)入臨床研究及上市的重要環(huán)節(jié)。生殖Ⅱ段,即胚胎-胎仔發(fā)育毒性試驗(yàn),研究胚胎從著床到硬腭閉合期間給藥,受試藥物是否具有胚胎毒性或致畸性。胚胎-胎仔發(fā)育毒性試驗(yàn)需選用兩種哺乳動(dòng)物,一般非嚙齒類選擇家兔[1]。國內(nèi)外關(guān)于家兔
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