托吡酯对妊娠小鼠的不良作用及叶酸对其干预效果

Ill effects of topiramate on pregnant mouse and intervention study of folic acid

【目的】观察托吡酯对妊娠小鼠的不良作用,探讨叶酸对其不良效应的干预效果。【方法】将100只雌性和50只雄性小鼠随机分为5组(雌雄比例2:1),分别为:空白对照组(灌胃蒸馏水,10 ml/kg);托吡酯低剂量组(50 mg/kg);托吡酯高剂量组(100 mg/kg);托吡酯低剂量与叶酸联合用药组(50 mg/kg+0.07 mg/kg);托吡酯高剂量与叶酸联合用药组(100 mg/kg+0.07 mg/kg)。观察小鼠是否受孕、流产、畸形、死胎、每窝仔鼠数目及孕期增重情况等指标。【结果】与其他各组相比,高剂量组小鼠的受孕率下降,孕鼠的流产率、死胎率和畸胎率均上升,孕期增重和每窝正常仔鼠数目减少(P<0.05)。与低剂量组受孕率30%及低剂量+叶酸组受孕率50%相比,高剂量组受孕率20%及高剂量给药+叶酸组小鼠的受孕率35%,明显下降(P<0.05);与低剂量+叶酸组受孕率50%、死胎率8.7%和高剂量+叶酸组受孕率35%、死胎率9.8%相比,低剂量组受孕率30%、死胎率10.5%和高剂量组小鼠受孕率20%、死胎率28.5%,差异显著(P<0.05)。与低剂量+叶酸组第20天孕鼠体重(13.18±0.74)g及高剂量+叶酸组第20天孕鼠体重(12.15±0.50)g相比,低剂量组第20天孕鼠体重(10.99±1.29)g及高剂量组第20天孕鼠体重(9.54±0.08)g,差异显著(P<0.05)。【结论】托吡酯可导致妊娠小鼠妊娠意外增多,低剂量给药及补充叶酸可降低托吡酯不良作用。

【Objective】 The aim of this study was to observe the ill effects of topiramate on pregnant mice,and to explore the intervention effect of folic acid on ill effects.【Methods】100 female and 50 male mice were randomly divided into 5 groups（female： male=2：1）.the groups as follows,the mice of blank control group were given distilled water 10 ml/kg by gavage,the mice of low dose topiramate group were given topiramate 50 mg/kg by gavage,the mice of high were given topiramate 100mg/kg by gavage,the mice of low dose topiramate and folic acid group were given topiramate 50 mg/kg and folic acid 0.07 mg/kg by gavage,the mice of high were given topiramate 100 mg/kg and folic acid 0.07 mg/kg by gavage.The indexes including fertilization,abortion,monster,stillbirth,number of filial mice in each brood and the weight during pregnancy were observed among groups.【Results】Compared to mice in other groups,the mice in high dose group had lower pregnancy rate,higher rate of abortion,stillbirth and monster,decrease of weight gain during pregnancy and number of normal filial mice each brood（P 0.05）.Comparing the mice in low dose group（pregnancy rate：30%） and low dose with folic acid group（pregnancy rate：50%）with the mice in high dose group（pregnancy rate：20%） and high dose with folic acid group（pregnancy rate：35%）,the difference was noticeable（P 0.05）.Comparing the mice in high dose group with folic acid（pregnancy rate：35%;stillbirth rate 9.8%） and low dose with folic acid group（pregnancy rate：50%;stillbirth rate 8.7%）with the mice in high dose group（pregnancy rate：20%;stillbirth rate 28.5%）and low dose group（pregnancy rate30%：stillbirth rate 10.5%） the difference was noticeable（P 0.05）.Comparing the weight of the pregnant mice after 20 days in low dose with folic acid group[（13.18±0.74） g] and the mice high dose with folic acid group[（12.15±0.50） g] with the mice in low dose [（10.99±1.29） g] and the mice in high dose group[（9.54±0.08） g],the difference was noticeable（P 0.05）.【Conclusions】topiramate can lead to increase pregnant accident of pregnant mouse,and multiple low dose and supplement of folic acid can decrease the ill effects of topiramate.