金属硫蛋白与铅致子代鼠肝组织氧化损伤的关系  

The relationship between metallothionein and oxidative stress induced by lead in liver of mice offspring

作　　者：张敬旭[1] 符绍莲[1] 江河[1] 阮明[2] 张宝旭[2] 

机构地区：[1]北京大学公共卫生学院妇幼卫生学系,北京100083 [2]北京大学公共卫生学院卫生毒理学系,北京100083

出　　处：《中国职业医学》2003年第2期11-13,共3页China Occupational Medicine

摘　　要：目的　应用金属硫蛋白 (MT)基因敲除小鼠及野生型小鼠模型 ,探讨孕期铅暴露 ,新生子代鼠肝组织氧化损伤与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 ,染毒剂量分别为 0、10、3 0、90mg/kg(对照、低、中、高剂量组 ) ,子鼠出生后第 1天处死 ,取肝组织测定丙二醛 (MDA)、还原型谷胱甘肽 (GSH)含量及超氧化物歧化酶 (SOD)活性 ,同时测定肝组织中MT的含量及母鼠血铅含量。结果　宫内铅暴露使MT( +/ +)及MT( -/ -)新生子鼠肝组织MDA升高 ,SOD活性降低 ,与染铅剂量组间存在显著的剂量 效应关系 (P <0 0 1)。相同铅染毒剂量组间比较结果显示 ,对照组、低及中剂量染铅组MT( -/ -)子鼠肝组织MDA含量显著高于MT( +/ +)子鼠 ,差异具有显著性 (P <0 0 1)。随染铅剂量的增加 ,MT( +/ +)子鼠肝组织GSH含量单向性升高 ;而MT( -/ -)子鼠肝组织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。低及高剂量染铅组MT( +/ +)子鼠肝组织MT含量显著高于对照组 (P <0 0 1)。相同染铅剂量MT( -/ -)母鼠血铅水平显著高于MT( +/ +)母鼠 (P <0 0 1)。结论　MT的缺乏可使经孕期铅暴露的新生子鼠肝组织脂?Objective To study the relationship between the oxidative stress induced by lead during pregnancy and metallothionein(MT) in the offspring liver by using the model of mice with metallothionein(MT) gene knocked out and wild type. Methods 10, 30 and 90 mg/kg lead acetate was orally administrated to the pregnant mice with MT gene null and wild type mice with MT gene daily from the day 0 to the end of gestation. The litters were killed on the 1st day after birth. Levels of malondialdehyde(MDA), glutathione(GSH), MT and superoxide dismutase(SOD) activities in the newborn mice liver were determined. The content of lead in maternal blood was also determined. Results ①In the two types of newborn mice, levels of MDA increased while the activity of SOD decreased in the liver with lead exposure of pregnant mice. The changes showed dose dependent correlation with the dosage of lead exposure( P <0 01). The levels of MDA in MT(-/-) mice were significantly higher than those in MT(+/+) mice( P <0 01). ② As the dosage of lead increased, the content of GSH in MT(+/+) mice was elevated, while that in MT(-/-) mice firstly increased and then decreased. ③In the MT(+/+) mice liver, the levels of MT in the lowest and the highest dosage were significantly higher than those in the control. ④The levels of blood lead in MT(-/-) mice were significantly higher than those in MT(+/+) mice between the same dosage( P <0 01). Conclusion Lacking of MT in the offspring liver might enhance the lipid peroxidation induced by lead during pregnancy.

关 键 词：铅 金属硫蛋白 转基因 脂质过氧化 

分 类 号：R135.11[医药卫生—劳动卫生]