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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 ,而大剂量及与丙戊酸钠联合用药时影响较大
Objective To study the toxicity of Topiramate (TPM) on the development of rat embryos. Methods Pregnant SD rats were randomly divided into five groups. In the experimental group, TPM 40 mg / kg, TPM 80 mg / kg and TPM 40 mg / kg + VPA 30 0 mg / kg were orally administered orally from 6th to 15th day of gestation. Negative control group orally by the same period to give the same amount of distilled water. Positive control group on the 11th day of pregnancy a single intraperitoneal injection of cyclophosphamide (CP) 10mg / kg. Pregnant rats were sacrificed on the 20th day of gestation, and the live births, stillbirths and the number of fetuses were observed and analyzed. Results The body weight of the TPM 4 0mg / kg group, 80mg / kg group and TPM 40mg / kg + VPA 30 0mg / kg group were 89.6 ± 16.5 and 74.8 ± 10.7 ), (91.5 ± 2.03) g, which were significantly lower than those in the negative control group (10 9.5 ± 14.2 g) (t = 2.9, 6.4, .0 1, <0 .0 0 1 and <0 .0 5). The average body weight, body length and tail length of the offspring rats were significantly decreased. The stillbirth rate and the absorption rate of the three TPM groups increased and the number of live births decreased by 96%, 88% and 86% respectively, while the negative control group was 97% The implantation ratio of live fetus and stillborn fetus + fetus fetus was significant at high dose and in combination group with VPA (χ2 = 7.7,9.95, P <0.01). Abdominal umbilical hernia, short tail increased. Conclusions TPM has little effect on the development of embryos at low doses, while the effects of high dose and combination with sodium valproate are significant