卡马西平联合丙戊酸钠致妊娠小鼠不良反应及叶酸干预对不良反应的影响

Analysis on adverse reaction of carbamazepine combined with sodium valproate on pregnant mice and the intervention effect of folic acid on the adverse reaction

【目的】观察卡马西平联合丙戊酸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=2:1):(1)空白对照组(灌胃蒸馏水,10 ml/kg)。(2)卡马西平给药组(66.7 mg/kg)。(3)卡马西平+丙戊酸钠联合给药组(卡马西平66.7 mg/kg+丙戊酸钠150 mg/kg)。(4)卡马西平+叶酸联合给药组(卡马西平66.7 mg/kg+叶酸0.07 mg/kg)。(5)卡马西平+丙戊酸钠+叶酸联合给药组(卡马西平66.7 mg/kg+丙戊酸钠150 mg/kg+叶酸0.07 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,卡马西平+丙戊酸钠联合给药组小鼠的受孕率(10.0%)下降,孕鼠的流产率(50%)、死胎率(53.8%)和畸胎率(9.1%)均上升,孕期增重[10 d:(2.16±0.06)g;20 d(9.56±0.06)g]和每窝正常仔鼠数目(4.02±1.40)减少(P<0.05)。与卡马西平给药组和卡马西平+叶酸联合给药组相比,卡马西平+丙戊酸钠联合给药组和卡马西平+丙戊酸钠+叶酸联合给药组小鼠的受孕率下降、死胎率上升(P<0.05);与卡马西平+叶酸联合给药组和卡马西平+丙戊酸钠+叶酸联合给药组相比,卡马西平组和卡马西平+丙戊酸钠联合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】卡马西平+丙戊酸钠联合给药可导致妊娠小鼠妊娠意外增多,单一卡马西平给药及补充叶酸可降低卡马西平联合丙戊酸钠的不良作用。

[Objective]To observe the adverse reaction of carhamazepine＋sodium valproate on pregnant mice, and to explore the intervention effect of folio acid on the adverse reaction. [Methods] 100 female and 50 male mice were randomly divided into 5 groups （remale：male=2：1）. The groups were assigned and treated as follows. （1）The mice of blank control group were given distilled water 10 ml/kg by garage. （2）The mice of single dose earhamazepine group were given earhamazepine 66.7 mg/kg by garage. （3）The mice of secondary dose carbamazepine＋sodium valproate group were given carbamazepine 66.7 mg/kg and sodium valproate 150 mg/kg by gavage. （4）The mice of secondary dose carbamazepine＋ folio acid group were given earbamazepine 66.7mg/kg and folio, acid 0.07mg/kg by garage. （5） The mice of three doses of earbamazepine＋sodium valproate ＋ folio acid group were given carbamazepine 66.7 mg/kg sodium valproate 150 mg/kg and folio acid 0.07 mg/kg by gavage. The indexes include the rate of fertilization, abortion, stillbirth and monster, the number of baby mice and decrease of weight gain during pregnancy. [ Results ] Compared to mice in other groups, the mice in earbamazepine＋ sodium valproate group had lower pregnancy rate, higher rate of abortion, stillbirth and monster, decrease of weight gain during pregnancy and nmnber of normal filial mice in each brood（P 〈 0.05）. Compared to mice in carbamazepine group and secondary dose carbamazepine＋ folio acid group, the mice in carbamazepine＋sodium valproate group and earbamazepine＋sodium valproate＋folie acid group had lower pregnant rate and higher stillbirth rate respectively（P 〈 0.05）. [Conclusions]Carbamazepine ＋sodium valproate can lead to increase pregnant accident of pregnant mouse, and single carbamazepine dose and supplement of folic acid can decrease the adverse effects of carbamazepine ＋sodium valproate.