摘要
目的 研究妥泰 (topiramate,TPM)对大鼠胚胎发育的毒性。 方法 将妊娠SD大鼠随机分为五组。实验组于妊娠 6～ 15d经口灌胃给予TPM 4 0mg/kg ,TPM 80mg/kg和TPM4 0mg/kg+丙戊酸钠 (VPA) 30 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 11天一次性腹腔注射环磷酰胺 (CP) 10mg/kg。于妊娠第 2 0天处死孕鼠 ,观察分析活胎、死胎和吸收胎数、仔鼠身体外形畸形及有关发育指标。 结果 实验组的TPM 4 0mg/kg组、80mg/kg组和TPM 4 0mg/kg +VPA 30 0mg/kg组母鼠体重增长分别为 ( 89.6± 16 .5 )、( 74 .8±10 .7)、( 91.5± 2 0 .3)g ,显著低于阴性对照组 ( 10 9.5± 14 .2 ) g(t值分别为 2 .9、6 .4、2 .3,P值分别为 <0 .0 1,<0 .0 0 1和 <0 .0 5 )。仔鼠的平均体重、身长、尾长指标明显降低 ;上述TPM三组的死胎率和吸收胎率增加 ,活胎数减少 ,分别为 96 %、88%、86 % ,阴性对照组为 97% ,植入数中活胎和死胎+吸收胎间的构成比 ,在大剂量及与VPA联合用药组差异有非常显著性 ( χ2 值分别为 7.7、9.95 ,P均 <0 .0 1)。仔鼠脐疝、短尾增多。 结论 TPM在小剂量时对胚胎的发育影响较小 。
Objective To study the toxicity of topiramate (TPM), an antiepileptic drug, on embryonic development in rats. Methods Fifty one female pregnant rats were divided into five groups. TPM 40 mg/kg, TPM 80 mg/kg and TPM 40 mg/kg+ valproate acid( VPA) 300 mg/kg were given to group A,B and C respectively by gavage on day 6～15 through gestation. The negative control group(D) were administered with distilled water and the positive control group(E) were treated with cyclophosphomide (CP) (10 mg/kg on day 11, ip). All animals were sacrificed on day 20. The survival, dead and absorbed fetus was calculated. The parameters of embryonic and fetal development were analyzed and external abnormality was examined. Results Maternal body weight gain in group A,B and C [(89.6±16.5) g, (74.8±10.7) g, (91.5±20.3) g] was significantly lower than that of group D [(109.5±14.2) g ( P <0.01,<0.001,<0.05 respectively)]. The mean body weight, body length and tail length of the fetus were significantly reduced compared with those in group D. The percentage of living fetus were 96%, 88 %, 86 % in group A,B and C which was lower than the negative control (98 %). Significant difference was found in the rate of survival fetus , dead and absorbed fetus between group B and C ( P <0.01). More umbilical hernia and short tail were found in experimental group. Conclusions Small dose of TPM had minimal effect on the embryonic development of rats. But the adverse effect was significant when using higher dose of TPM or combined with VPA.
出处
《中华围产医学杂志》
CAS
2004年第5期297-300,共4页
Chinese Journal of Perinatal Medicine
关键词
抗癫痫药
妥泰
大鼠
胚胎发育毒性
Fructose
Antiepileptic drug
Toxicity tests
Fetal growth restriction
Rats
