金属硫蛋白降低铅致新生仔鼠脑组织的氧化损伤

目的　应用金属硫蛋白基因敲除小鼠模型 ,研究孕鼠铅暴露 ,新生仔鼠脑组织氧化损伤与金属硫蛋白 (MT)间的关系。方法　采用整体动物实验 ,于金属硫蛋白基因敲除小鼠 [MT(- / - ) ]和野生型小鼠[MT(+/ +) ]孕第 0天至妊娠结束进行醋酸铅灌胃染毒 ,仔鼠出生后第 1天处死 ,取脑组织测定丙二醛(MDA)、还原型谷胱甘肽 (GSH)含量及超氧化物歧化酶 (SOD)活力 ,同时测定脑组织中MT的含量。结果　宫内铅暴露使MT (+/ +)及MT (- / - )新生仔鼠脑组织MDA含量升高 ,SOD活力降低 ,与染铅剂量间存在明显的剂量 -效应关系 (P <0 0 1)。相同醋酸铅染毒剂量间比较结果显示 ,对照组、低及中剂量染铅组MT (- / - )仔鼠脑组织MDA含量明显高于MT (+/ +)仔鼠 ,差异具有显著性 (P <0 0 1)。随染铅剂量的增加 ,MT (+/ +)仔鼠脑组织GSH含量单向性升高 ;而MT (- / - )仔鼠脑组织GSH含量的变化为非单向性 ,表现为低、中剂量升高 ,高剂量时下降的趋势。高剂量染铅组MT (+/ +)仔鼠脑组织MT含量明显高于对照组 (P <0 0 1)。结论　MT在体内铅的转运、代谢乃至解毒方面具有一定作用 ,MT的缺乏可使铅引起的脑组织脂质过氧化反应增强 ,进一步加重铅的神经发育毒性。

Decrease of Lead Induced Oxidative Damage of the Newborn Mice Brain Tissue by Metallothionein

Objective To investigate the relationship between the oxidative stress induced by lead during pregnancy and metallothionein(MT)in offspring brain using the model of mice with MT gene knocked out.Methods The mice with MT gene null[MT(-/-)]and wild mice with MT gene[MT(+/+)]were treated with lead acetate through enteron from the day 0 to the end of gestation.The litter was sacrificed one day after the birth.The levels of malondialdehyde(MDA), glutathione(GSH),MT and superoxide dismutase(SOD)activity in the newborn mice brain were determined.The contents of lead in maternal blood were also determined.Results In these two types of mice,lead in pregnant mice enhanced the level of MDA in brain,and decreased the SOD activity.The changes were dose dependent to lead (P<0 01).In the same dose,levels of MDA in MT(-/-)mice were significantly higher than those in MT(+/+)mice(P<0 01).Contents of GSH in MT(+/+)mice increased with the dose of lead,and that in MT(-/-)mice increased first and then decreased.In the MT(+/+) mice brain,levels of MT in the highest dose were significantly higher than those in control.Conclusions MT may play some roles in aspects of transportation,metabolism and detoxification.Shortage of MT in brain might enhance the lipid peroxidation induced by lead,which will further enhance the neurotoxicity in the development of brain.