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目的观察托吡酯(topiramate,TPM)对妊娠小鼠的胚胎毒性作用,探讨不同剂量叶酸(folic acid,FA)对其干预的效应。方法小鼠随机分为5组,每组雌雄比例2:1,分别为空白对照组,TPM组,TPM+低剂量FA组,TPM+中剂量FA组,TPM+高剂量FA组。上述各组小鼠于分组后次日,雌性鼠开始灌胃各药物,按上述方法给药,直至妊娠结束。以阴栓出现日为妊娠零天,观察小鼠生殖能力、生长发育、畸形等指标。结果 TPM对小鼠有胚胎毒性作用,补充不同剂量的FA有不同的拮抗效应。低剂量FA并不能有效干预这种毒性作用,而中剂量FA仅在胎鼠生长发育方面有一定的干预作用,高剂量FA拮抗TPM毒性作用的效果更明显。结论 TPM对小鼠胚胎有毒性作用,补充高剂量FA可有效的干预。
Objective To observe the embryotoxic effects of topiramate (TPM) on pregnant mice and to explore the effect of different doses of folic acid (FA) on it. Methods Mice were randomly divided into 5 groups: control group, TPM group, TPM + low dose FA group, TPM + medium dose FA group and TPM + high dose FA group. The mice in the above groups were administered the drugs on the day following the grouping, and the females were administered with the above method until the end of pregnancy. The day of vaginal suppository was zero day of pregnancy, and observed the reproductive ability, growth and development, deformity and other indicators of mice. Results TPM had embryotoxic effects in mice, and different doses of FA supplemented with different antagonistic effects. Low doses of FA can not effectively interfere with this toxic effect, while the middle dose of FA only in fetal growth and development have a certain intervention, high doses of FA antagonistic effect of TPM toxicity more pronounced. Conclusion TPM has toxic effects on mouse embryos and supplementation with high-dose FA may be an effective intervention.