【摘要】 目的:探索维甲酸(retinoic acid,RA)不同剂量诱发SD大鼠胚胎畸形的效果,为药物和化合物致畸试验的阳性对照品提供依据。方法:将SD大鼠孕鼠随机分为4组,即玉米油溶剂对照组,50,100和150mg·kg-1维甲酸组。各组在孕d 10灌胃(ig)给药1次,孕d 20处死孕鼠,观察胚胎外观畸形发生情况。结果:50 mg·kg-1及以上剂量组的维甲酸诱导SD大鼠胚胎出现明显的多发性畸形,致畸率为100%。畸形主要表现为下颌缺失、脊柱裂、眼球突出、足内翻、并肢、无尾或短尾、身材短小等,偶见脐膨出和全身水肿。维甲酸各组畸形的表型和各类畸形发生率呈现高度的一致性和可重复性,3个剂量组间的胚胎畸形率无显著差异(P<0.05),但畸形程度随剂量增高而加重。100和150 mg·kg-1剂量组出现明显的吸收胎或死胎,吸收胎率和死胎率随剂量增高而升高。结论:50 mg·kg-1维甲酸在孕d 10 ig给药,对SD大鼠有明显的致畸作用,且不会增加吸收胎率和死胎率。在本研究条件下50 mg·kg-1维甲酸为较理想的致畸剂量。更多还原

【Abstract】 Objective: To explore teratogenic effects of different doses of retinoic acid(RA) in SD rats,and provide scientific basis for selecting positive control drug of teratogenicity tests. Methods: Pregnant SD rats were randomly allocated into 4 groups: 50 mg·kg-1 RA group,100 mg·kg-1 RA group,150 mg·kg-1 RA group and corn oil group. They were administered via gavage with RA at gestation date(GD) 10 with doses of 50,100,150 mg·kg-1 and corn oil for four group. The multiple external abnormalities in rat embryos were observed and recorded at GD 20 after pregnant rats were sacrificed. Results: Multiple external abnormalities in rat embryos were clearly observed in all three RA-treated groups with teratogenetic rate of 100%. The main abnormalities included agnathia,rachischisis,exophthalmos,strephenopodia,symmelia,anury or short tail,short or small fetus. Omphalocele and hyposarca could be observed occasionally. The phenotype and occurrence rate of abnormalities in the three RA-treated groups were highly consistent and repeatable. There was no significant difference in the rate of embryo abnormalities in the three dose groups(P < 0. 05),but the degree of abnormality increased with the dose. Significant absorption or stillbirth were observed in 100 and 150 mg·kg-1 RA-treated groups,and the rate of absorption andstillbirth increased with the dose. Conclusion: 50 mg·kg-1 RA could induce significant teratogenic effects in SD rats with no increasing rates of absorption and stillbirth. Under the current experimental conditions,the 50 mg·kg-1 RA was considered to be the optimized dose for rat teratogenicity test.更多还原