目的:考察3种抗癫痫药干预对孕鼠生殖相关激素的影响。方法:孕鼠随机分为对照组、癫痫模型组、卡马西平组、丙戊酸钠组和托吡酯组5组,每组10只。对照组和癫痫模型组灌胃给予生理盐水,卡马西平组灌胃给药20 mg·kg-1·d-1,丙戊酸钠组灌胃给予丙戊酸钠200 mg·kg-1·d-1,托吡酯组给予托吡酯20 mg·kg-1·d-1,连续灌胃20天。结果:5个组别孕鼠死胎情况比较,差异无统计学意义(P>0.05),分娩孕鼠对照组最多,产仔数最多,癫痫组大鼠的分娩孕鼠较少,产仔数少,其中丙戊酸钠组的娩孕鼠和产仔数最少,组间比较差异有统计学意义(P<0.05)。5个组别存活的仔鼠无畸形,与对照组比,4组癫痫孕鼠胎盘重量较轻,仔鼠的体重较轻、体长和尾长较短(P<0.05)。对照组、癫痫模型组和托吡酯组的卵巢脏器系数相当,丙戊酸钠组的卵巢脏器系数较小(P<0.05),卡马西平组的卵巢脏器系数较大。与对照组比,模型组的E2、T和PRL较高(P<0.05),FSH降低(P<0.05),LH无显著差异(P>0.05),5个组间LH比较,差异无统计学意义(P>0.05)。与模型组比,卡马西平组E2升高(P<0.05),丙戊酸钠组E2降低(P<0.05),托吡酯组E2无显著差异(P>0.05),与对照组比,丙戊酸钠组E2降低,托吡酯组E2无显著差异(P>0.05)。与模型组比,卡马西平组和托吡酯组T比较,差异无统计学意义(P>0.05),丙戊酸钠组T升高(P<0.05),与对照组比,卡马西平组和托吡酯组T无显著差异比较,差异无统计学意义(P>0.05),癫痫孕鼠给予抗癫痫药组与对照组FSH无显著差异,略高于模型组。与模型和对照组比,丙戊酸钠组PRL显著降低(P<0.05),与模型组比,卡马西平和托吡酯组的PRL比较,差异无统计学意义(P>0.05),4组癫痫的血清免疫球蛋白Ig G和Ig A较低(P<0.05)。与对照组比,癫痫组的仔鼠脑海马CA1区的神经元细胞缺失,细胞解体,健康细胞明显减少,各个抗癫痫组CA1区存在不同程度的神经元细胞少量缺失和健康细胞减少,以丙戊酸钠组最为明显。结论:对于癫痫孕鼠,测定生殖内分泌系统分泌的激素水平的变化可预生殖结局。卡马西平、丙戊酸钠和托吡酯对癫痫孕鼠的生殖相关激素和仔鼠海马CA1区神经元细胞均有不同程度的影响,但孕妇应用丙戊酸钠和卡马西平还需谨慎。 Objective: To investigate the effects of three antiepileptic drugs on reproductive-related hormones in pregnant rats. Methods: Pregnant mice were randomly divided into control group, epilepsy model group, carbamazepine group, sodium valproate group and topiramate group, with 10 rats in each group. Control group and epilepsy model group were given intragastric administration of saline, carbamazepine group intragastric administration of 20 mg · kg-1 · d-1, sodium valproate group intragastric administration of sodium valproate 200 mg · kg-1 · d-1, topiramate given topiramate 20 mg · kg-1 · d-1, continuous gavage for 20 days. Results: There was no significant difference in the stillbirth of the five groups (P> 0.05). The pregnant women in the five groups had the highest number of littermates and the largest number of littermates. There were fewer pregnant rats and fewer litters in epileptic rats , Among which the mice in the valproate group had the least number of pregnant rats and litter size, the difference between the two groups was statistically significant (P <0.05). There was no deformity in the offspring of the 5 groups. Compared with the control group, the weight of the placenta in the 4 groups of epileptic pregnant rats was lighter, the weight of the offspring was lighter, and the body length and tail length were shorter (P <0.05). The control group, epilepsy model group and topiramate group had similar ovarian organ coefficient, valproate sodium group had lower ovarian organ coefficient (P <0.05), and carbamazepine group had larger ovarian organ coefficient. Compared with the control group, E2, T and PRL in model group were higher (P <0.05), FSH was lower (P <0.05), LH was not significantly different (P> 0.05) Significance (P> 0.05). Compared with the model group, E2 in carbamazepine group increased (P <0.05), E2 in valproate group decreased (P <0.05), E2 in topiramate group had no significant difference (P> 0.05) E2 in the sodium group decreased, while there was no significant difference in the topiramate group (P> 0.05). Compared with the model group, there was no significant difference in T between carbamazepine group and topiramate group (P> 0.05), and T in valproate group was significantly higher than that in the control group (P <0.05) Topiramate group T no significant difference, the difference was not statistically significant (P> 0.05), epilepsy pregnant rats given anti-epileptic drug group and control group FSH no significant difference, slightly higher than the model group. Compared with the model and control group, the PRL in sodium valproate group was significantly lower than that in the model group (P <0.05), and there was no significant difference in the PRL between the carbamazepine group and the topiramate group (P> 0.05) Serum immunoglobulin Ig G and Ig A were lower (P <0.05). Compared with the control group, the neuronal cells in hippocampal CA1 region of the epilepsy group were missing, the cells disintegrated and the number of healthy cells was significantly decreased. There was a small amount of neuronal cell loss and healthy cells decrease in CA1 region in each epilepsy group, The valerate group was the most obvious. CONCLUSIONS: For epileptic pregnant rats, changes in the hormone levels secreted by the reproductive endocrine system can be measured to predict prenatal outcome. Carbamazepine, sodium valproate and topiramate exert different effects on reproductive-related hormones and hippocampal CA1 neurons in pregnant rats, but pregnant women should be cautious when using sodium valproate and carbamazepine.