不同剂量叶酸对托吡酯致胚胎毒性作用的干预研究

INTERVENTION OF DIFFERENT DOSES OF FOLIC ACID TO EMBRYO TOXICITY EFFECTS INDUCED BY TOPIRAMATE

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 explore the intervention of different doses of folic acid to teratogenic effects induced by topiramate of pregnant mice. Methods The proportion of female and male mice was 2：1 ,the mice were divided into five groups randomly： the control group, topiramate group, topiramate ＋ folie acid low dose group, topiramate ＋ folic acid in mid-dose group, topiramate ＋ folic acid high-dose group. The female started to fill the stomach of each drug after the next day, according to the method of administration until the end of pregnancy. With the vaginal plug appeared on gestational day zero, the mice reproductive ability, growth and development, deformity and so on were observed. Results Topiramate in mice had teratogenic role definitely, supplemented with different doses of folic acid showed different antagonistic effect. Low dose of folic acid was not effective intervention for this toxic effect, medium-dose folic acid showed certain intervention effect in fetal growth and development, but the toxic effects of high dose folic acid proved antagonist topiramate significantly. Conclusion Topiramate in mice has teratogenic role definitely, supplement high dose folic acid can effectively intervene.