大鼠出生前接触苯妥英和褪黑素对仔代反射功能发育及自发运动的影响

Effects of prenatal exposure to phenytoin and melatonin on the development of reflex function and locomotive activities of rat pups

目的 :探讨苯妥英 (DPH)神经发育毒性与胚胎脑组织中自由基产生和氧化应激反应的关系。方法 :Wistar孕鼠于妊娠d 11～ 14经 0 ,10 0 ,2 0 0mg·kg-1DPH或合并 4 0mg·kg-1褪黑素 (MT)染毒处理 ,研究MT对DPH的仔代反射功能发育及自发运动损害作用的拮抗效应。结果 :孕鼠在染毒期及染毒后增重下降 ,仔代体重减轻 ,哺乳期死亡率增高 ;DPH染毒仔鼠的转身运动增多 ,空中翻正反射及游泳能力发育延迟 ,成年后行走次数、站立次数、刻板动作等自发活动增多 ,旋转手比率增多 ,对阿朴吗啡“激发”反应性增强。MT和DPH合并处理可明显拮抗上述DPH仔鼠的行为异常。结论 :氧化性损伤在DPH神经发育毒性发生中发挥重要作用 ,而MT可拮抗其毒性作用。

AIM: To explore the relationship between the developmental neurotoxicity (DNT) induced by prenatal phenytoin(DPH)exposure and free radicals and oxidative stress initiated in the embryonic brain. METHODS: Pregnant Wistar rats were administered DPH by gavage on gestation days (GD) 11-14 in doses of 0,100, 200 mg·kg -1 and/or 40 mg·kg -1 MT (melatonin). RESULTS: DPH treated dams showed a dose related decrease in weight gain throughout the treatment period. Offspring had significantly lowered birth weight along with increased mortality. During the neonatal period,the pups exposed in uterus to DPH showed a significant increase in pivoting locomotion,and delayed in air righting reflex and swimming development. As adults,these pups showed an increased ambulation,rearing,stereotype events and rotational behavior. Furthermore,prenatal DPH exposure resulted in a dose-response shift to the left for locomotor activity of F_1 DPH pups after stimulated by 0.2 and 2.0 mg·kg -1 apomorphine. CONCLUSION: Co-administration of MT and DPH to dams significantly antagonized or protected most of the postnatal adverse effects induced by prenatal DPH exposure in F_1 pups,which suggest that DNT induced by prenatal DPH exposure may be evoked and mediated via oxidative stress.