苯妥英钠对妊娠小鼠的致畸作用及叶酸的干预影响分析

Analysis on the teratogenic effect of phenytoin sodium on pregnant mice and the intervention of folic acid

目的:观察苯妥英钠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:①空白对照组(灌胃蒸馏水,10 ml/kg);②苯妥英钠单次剂量组(50mg/kg);③苯妥英钠二次给药组(上、下午各为25 mg/kg);④苯妥英钠单次剂量与叶酸联合用药组(50 mg/kg+0.07 mg/kg);⑤苯妥英钠二次给药与叶酸联合用药组(25 mg/kg+0.035 mg/kg)。观察小鼠是否受孕、流产、畸形、死胎、每窝仔鼠的数目及孕期增重情况等指标。结果:与其他各组相比,单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)。与二次给药组和二次给药与叶酸组相比,单次剂量组和单次剂量与叶酸组小鼠的受孕率下降、死胎率上升(P<0.05);单次剂量与叶酸组和二次给药与叶酸组相比,单次剂量组和二次给药组小鼠的受孕率下降、死胎率上升、孕期增重减少(P<0.05)。结论:苯妥英钠可导致妊娠小鼠妊娠意外的增多,小剂量多次给药以及补充叶酸可降低苯妥英钠的不良作用。

Objective：To observe the adverse effect of phenytoin sodium on pregnant mice,explore the intervention of folic acid. Methods：100 female mice and 50 male mice were randomly divided into 5 groups（female mice∶male mice=2∶1）： blank control group（the mice were treated with pouring distilled water into the stomach）,single dose phenytoin sodium group（the mice were treated with phenytoin sodium,50mg/kg）,secondary dose phenytoin sodium group（the mice were treated with phenytoin sodium,25 ml/kg in the morning and 25 ml/kg in the afternoon）,single dose phenytoin sodium and folic acid group（the mice were treated with phenytoin sodium（50 mg/kg） and folic acid（0.07 mg/kg））,secondary dose phenytoin sodium and folic acid group（the mice were treated with phenytoin sodium（25 mg/kg） and folic acid（0.035 mg/kg））.The indexes including conception or not,abortion or not,malformation,stillbirth,the number of neonatal mice in each brood and body weight gain during pregnancy were observed. Results：Compared with the other groups,the pregnancy rate in single dose phenytoin sodium group decreased,the abortion rate,stillbirth rate and incidence of fetal malformation increased,body weight gain during pregnancy and the number of neonatal mice in each brood decreased（P0.05）.Compared with secondary dose phenytoin sodium group,secondary dose phenytoin sodium and folic acid group,the pregnancy rates in single dose phenytoin sodium group,single dose phenytoin sodium and folic acid group decreased,the stillbirth rates increased（P0.05）.Compared with single dose phenytoin sodium and folic acid group,secondary dose phenytoin sodium and folic acid group,the pregnancy rates in single dose phenytoin sodium group,secondary dose phenytoin sodium group decreased,the stillbirth rates increased,body weight gains decreased（P0.05）. Conclusion：Phenytoin sodium can lead to increase of pregnant accidents of pregnant mice,multiple low dose supplement of folic acid can decrease the adverse reactions of phenytoin sodium.