减少奥卡西平对妊娠小鼠不良作用的实验研究

摘要目的观察奥卡西平单次给药与分次给药对妊娠小鼠的影响及叶酸对其诱发小鼠发生妊娠意外的干预效果，探讨减少奥卡西平所致不良作用的干预措施。方法将150只小鼠随机分为5组（每组30只，雌雄比例2：1），分别为：①对照组（灌胃纯化水10 mL•kg－1），②奥卡西平单次给药组（单次灌胃奥卡西平150 mg•kg－1），③奥卡西平单次给药＋叶酸组（单次灌胃奥卡西平150 mg•kg－1 ＋叶酸0.07 mg•kg－1），④奥卡西平分次给药组（分次灌胃奥卡西平，上、下午各75 mg•kg－1），⑤奥卡西平分次给药＋叶酸组（分次灌胃奥卡西平，上、下午各75 mg•kg－1 ＋叶酸0.07 mg•kg－1）。观察小鼠受孕率、流产率、死胎吸收胎率、畸形率、每窝正常仔鼠的数目、妊娠期增重、小鼠血清叶酸含量等指标。结果奥卡西平单次给药组、单次给药＋叶酸组、分次给药组、分次给药＋叶酸组小鼠受孕分别为4，6，8，10只；死胎和吸收胎分别为3，4，5，6只；小鼠妊娠期增重、血清叶酸含量依次升高；奥卡西平无明显致畸作用。结论奥卡西平可导致妊娠小鼠妊娠意外的增加，但无明显致畸作用，小剂量分次给药及补充适量叶酸可降低其不良作用。

Experimental Study on Reducing the Adverse Effects of Oxcarbazepine in Pregnancy Mice

Objective To study the influence of oxcarbazepine administration at single or repetitive(multiple) dose in pregnant mice and the interference effects of folic acid on the unexpected adverse event induced by oxcarbazepine in pregnant mice,and to investigate the measures to reduce the adverse effects of oxcarbazepine in pregnant mice.Methods One hundred and fifty mice were randomly divided into 5 groups(n=30 of each group,ratio of female to male was 2:1).In control group,the mice were perfused with distilled water(10 mL·kg-1) in stomach;in single-dose oxcarbazepine group,the mice were perfused with oxcarbazepine(150 mg·kg-1) in stomach;in single-dose oxcarbazepine + folic acid group,the mice were perfused with oxcarbazepine(150 mg·kg-1) and folic acid(0.07 mg·kg-1) in stomach;in repetitive dose oxcarbazepine group,the mice were perfused with oxcarbazepine(75 mg·kg-1) in stomach in the morning and afternoon,respectively;in repetitive dose oxcarbazepine + folic acid group,the mice were perfused with oxcarbazepine(75 mg·kg-1) and folic acid(0.07 mg·kg-1) in stomach in the morning and afternoon.Conception rate,abortion rate,the absorptions and dead rate,aberration rate,number of normal newborn mice,weight increment during pregnancy,the content of serum folic acid were detected.Results The pregnancy rates of mice in oxcarbazepine single-dose group,oxcarbazepine single-dose + folic acid group,repetitive dose oxcarbazepine group,and repetitive dose oxcarbazepine + folic acid group were 20%,30%,40%,and 50%,respectively.The absorptions and dead rates were 18.8%,9.8%,11.6% and 9.2%,respectively.The weight increment during pregnancy and the contents of serum folic acid were increased in these groups in turn.No significant teratogenic effects caused by oxcarbazepine were found.Conclusion Oxcarbazepine can lead to unexpected adverse events in mice during pregnancy without significant teratogenic effects;multiple small dose of oxcarbazepine and supplement of folic acid can reduce the adverse effects.