抗癫痫药妥泰对大鼠胚胎骨骼发育影响的研究

Study on embryonic skeleton developmental influence of antiepileptic drug topiramate in rats

目的 研究妥泰 (TPM )高、低剂量单药及与丙戊酸钠 (VPA)合用对大鼠胚胎骨骼发育的影响。方法 采用妊娠雌性SD大鼠随机分为 5组。实验组 3组 ,于妊娠 6～ 15d分别经口灌胃给予TPM 4 0mg/kg ,TPM 80mg/kg和TPM 4 0mg/kg +VPA30 0mg/kg。阴性对照组同期经口灌胃给以等量的蒸馏水。阳性对照组于妊娠第 11d一次性腹腔注射环磷酰胺(CP) 10mg/kg。于妊娠第 2 0d处死孕鼠 ,将胎仔茜素红和阿利新蓝骨骼双染后 ,检查全身骨骼发育程度。结果 TPM高剂量组及与丙戊酸钠联合用组仔鼠骨骼发育迟缓 ,与阴性对照组相比有明显的差异。但TPM低剂量组无显著差异。结论 TPM在低剂量时对大鼠胚胎骨骼发育影响较小 ,而高剂量及与丙戊酸钠联合用药时影响较大。

Objective:To study the embryonic skeleton developmental effect of topiramate(TPM) in rats in low dosage or high dosage or in combination with valproate acid( VPA). Methods:Gravid female SD rats were divided randomly into five groups. The rats in the experimental groups were administered with TPM 40 mg/kg, TPM 80 mg/kg and TPM 40 mg/kg+VPA 300 mg/kg respectively by gavage on day 6 through 15 of gestation. The rats in the negative control group were administered with distilled water in the same way as in the experimental groups. And the rats in the positive control group were treated with cyclophosphomide (CP)at a dose of 10 mg/kg on day 11 of gestation by ip. All animals were sacrificed on day 20 of pregnancy. After double stained with alizarin red S and alcian blue, the rat fetal skeleton was examined.Results:The fetus showed ossification delay in experimental group compared with those in negative control group,and there didn't show significant difference in low dosage group, but in high dosage group and combination group did. Conclusions:The influence of TPM on the embryonic skeleton development of rats was small when administered in low dosage, but became obvious when administered in high dosage or in combination with VPA.