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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 study the reproductive toxicity and embryo malformation model of aspirin administered intragastrically in rats. Methods: SPF Wistar rats were randomly divided into blank control group, vitamin A group (positive control group) and aspirin group. The positive group received 12 800 μg · kg -1 retinol equivalent and aspirin dose 280 mg · kg -1, BW. The gavage was calculated according to 10.0 ml · kg -1 BW, while the control group was given the same volume of water for injection. Pregnant mice were dosed intragastrically every 7-16 days and sacrificed at 20 days of gestation. The embryonic development and fetal development indices were analyzed, and the appearance of deformity and deformity of the bone were examined. Results: Aspirin had effects on the reproductive capacity of pregnant rats (uterine weight and ovarian weight decreased, the average number of live births decreased, the live birth rate decreased and the stillbirth rate increased) (P <0.05). Aspirin had effects on the growth and development of the fetuses (P <0.05). The appearance of fetus was abnormal, such as systemic skin flushing and easy subcutaneous hemorrhage (P <0.05). Aspirin caused fetal bone abnormalities (abnormalities of sternum, vertebral anomalies , Rib abnormalities) (P <0.05). Conclusion: Aspirin produced embryo toxicity in large dose and obvious teratogenicity.