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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 effects of phenytoin on pregnant mice and to explore the intervention effect of folic acid on its adverse effects. Methods: 100 female and 50 male mice were randomly divided into 5 groups (sex ratio 2: 1): ① blank control group (intragastric administration of distilled water, 10 ml / kg); ② phenytoin single dose group (50 mg / kg); (3) phenytoin sodium secondary administration group (25 mg / kg on the morning and afternoon respectively); ④ single dose of phenytoin combined with folic acid (50 mg / kg +0.07 mg / kg) Phenytoin secondary administration combined with folic acid (25 mg / kg + 0.035 mg / kg). Observe whether the mice are conception, miscarriage, deformity, stillbirth, the number of litters and weight gain during pregnancy. Results: Compared with other groups, the conception rate of mice in single dose group decreased, the miscarriage rate, the stillbirth rate and the rate of teratogenicity in pregnant mice increased. The weight gain during pregnancy and the number of normal pups per litter decreased (P <0.05) . Compared with the secondary administration group and the secondary administration group and the folic acid group, the conception rate of the single dose group and the single dose and folic acid group mice decreased and the stillbirth rate increased (P <0.05). Compared with the folic acid group, Compared with the folic acid group, the conception rate, the stillbirth rate and the weight gain during pregnancy in the single dose group and the secondary administration group decreased (P <0.05). CONCLUSIONS: Phenytoin sodium can cause an unexpected increase of pregnancy in pregnant mice. The administration of multiple doses of small doses and folic acid supplementation may reduce the adverse effect of phenytoin sodium.