2,4-二氯苯氧乙酸对子代大鼠发育及脑组织的氧化损伤作用

Effects of 2,4-dichlorophenoxyacetic acid on offsprings' development and oxidative stress

目的:研究大鼠孕期和哺乳期暴露2,4-二氯苯氧乙酸(2,4-D)对子代发育及脑组织脂质过氧化的损伤作用。方法:Wistar大鼠于受孕后第2天开始经口灌胃染毒2,4-D(0、25、50和100 mg/kg)直至仔鼠出生后第21天,每天1次,连续42 d。期间检测仔鼠生理及早期神经行为发育指标。断乳1周后处死仔鼠检测脑组织丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量及谷胱甘肽过氧化物酶(GSH-Px)的活力。结果:与对照组相比,100 mg/kg剂量组仔鼠体质量从出生后14 d开始降低,50 mg/kg剂量组仔鼠体质量从出生后21 d开始降低,差异均有统计学意义(P<0.05),而其他各生理发育指标差异均无统计学意义(P>0.05)。神经行为测试中100 mg/kg剂量组仔鼠断崖回避、空中翻正及听觉惊愕的阳性发生率均明显低于对照组(P<0.05),出现神经行为发育迟缓。50和100mg/kg剂量组仔鼠脑组织中MDA含量升高,100 mg/kg剂量组仔鼠脑组织GSH含量及GSH-Px的活性下降,与对照组相比差异均有统计学意义(P均<0.05)。结论:大鼠孕期和哺乳期暴露2,4-D致子代神经发育迟缓可能与2,4-D引起脑组织脂质过氧化损伤有关。

OBJECTIVE： To study the effects of 2,4-dichlorophenoxyacetic acid（2,4-D） on early neurobehavior development and oxidative stress in offsprings. METHODS：Pregnant Wistar rats were treated with 2,4-D by gavage,in doses of 0,25,50,100 mg/kg once a day from gestation day 2 until postnatal day 21. Then the early physiological and neurobehavioral indexes in the offsprings were measured. The levels of MDA,GSH and the GSH-Px activities in brain tissues of newborn rat were determined. RESULTS：The weights of offspring in the 100 mg/kg 2,4-D group were lower than in control after postnatal day 14（P〈0.05） and the weights of offspring in the 50 mg/kg 2,4-D were lower than in control after postnatal day 21（P〈0.05）. The physiologic markers including eye opening,pinna detachment,hair growth,tooth growth etc in all treated groups were not affected in contrast to the control group,cliff avoidance,mid-air righting and acoustic startle in the 100 mg/kg 2,4-D group were delayed（P〈0.05）. The level of GSH and GSH-Px activities decreased in the 100 mg/kg 2,4-D group,while the level of MDA was elevated in the 50 and 100 mg/kg 2,4-D groups. CONCLUSION：Early neurobehavioral development of offspring rats could be impaired by 2,4-D due to its disturbance to the homeostasis of oxidation and anti-oxidation system.