阿司匹林建立大鼠胚胎畸形模型研究

Study on Teratogenic Effects of Aspirin on Embryos of Rats

目的:研究阿司匹林灌胃建立大鼠的生殖毒性和胚胎畸形模型。方法:SPF级Wistar大鼠随机分成空白对照组、维生素A组(阳性对照组)和阿司匹林组,阳性组的剂量为12 800μg·kg^(-1) BW视黄醇当量,阿司匹林的剂量为280 mg·kg^(-1),BW。灌胃量按10.0 ml·kg^(-1) BW计算,对照组灌胃给予同体积的注射用水。孕鼠于7～16 d每d灌胃给药,妊娠20 d处死,分析其胚胎发育指标与胎仔发育指标,检查有无外观畸形和骨肋畸形。结果:阿司匹林对孕鼠生殖能力有影响(子宫重量和卵巢重量降低,平均活胎数减少,活胎率降低,死胎率升高)(P<0.05);阿司匹林对胎仔生长发育有影响(活胎体重降低、活胎身长缩短、胎盘重量降低)(P<0.05),胎鼠外观出现异常,如全身皮肤潮红,易皮下出血(P<0.05);阿司匹林引起胎仔骨骼发育异常(胸骨异常,脊椎骨异常,肋骨异常)(P<0.05)。结论:在规定剂量阿司匹林产生的胚胎毒性作用大,致畸作用明显。

Objective： To observe the reproductive toxicity and teratogenic effect of aspirin in rats by stomach-perfusion. Method： SPF wistar rats were randomly divided into negative control group, positive control group and aspirin group with 10.0 ml . kg- 1 BW gas- tric perfusion, while the control group received only the same distilled water. The rats were administrated with drugs on the 7-16th day of gestation, and the pregnant rats were dissected at 20th day after pregnancy to the indexes of embryonic and fetal development were analyzed and the appearance and bones malformation were inspected. Result： Compared with normal group, aspirin could decrease the weight of fetal mouse, uterus and ovary and the average number of survived fetus, and lower live fetus rate while higher dead fetus rate （ P 〈 0.05 ）. It also could reduce live fetus weight, body length and placental weight （ P 〈 0.05 ） ; abnormal appearance, such as whole skin flushing, subcutaneous hemorrhage （ P 〈 0.05 ） were discovered. Stimuha-neously, abnormal conditions were appeared in sternum, vertebral and ribs （P 〈 0.05）. Conclusion： Aspirin could cause high embryotoxicity and significant teratogenic effects with regulated dosage. And it can be used as positive teratogen in animal experiments.