母源性铅接触对子代鼠肝微粒体药酶活性的影响

目的 :观察给母鼠孕期及哺乳期饮用不同剂量的铅水后 ,其子代鼠肝微粒体药酶活性的变化。结果 :给母鼠饮用小剂量铅水 (5 0 0 μg/L ,超过WHO规定的饮用水标准 5倍 ) ,其子代 4周龄鼠肝铅含量明显增加 ,氨基比林脱甲基酶 (AMD)、谷胱甘肽 S 转移酶 (GST)活性明显降低 ,P45 0含量及细胞色素C还原酶 (NADPH C)、苯胺羟化酶(ANH)无明显变化 ,子代 8周龄鼠 (既铅负荷排除 4周后 )与正常子代鼠相比各药酶活性均无显著差异 ;给母鼠饮用大剂量铅水 (5 0 .0mg/L ,超过WHO规定的饮用水标准 5 0 0倍 ) ,其子代鼠出生 4周后各药酶活性显著低于正常子代鼠 ,P45 0含量及NADPH C、ANH、AMD、GST活性分别为正常 4周龄鼠的 5 8.0 %、5 2 .8%、81.0 %、2 7.9%、5 0 .2 % ,其中对AMD活性的影响最大 ;8周后 ,肝铅含量可恢复正常 ,但与正常 8周龄鼠相比 ,肝药酶活性仍显著低于正常。结论 :在大剂量母源性铅接触情况下 ,即使在铅负荷排除较长时间后 ,肝铅含量恢复正常时 ,肝药酶活性仍不能恢复至正常水平 ,表明母源性铅接触对子代生物转化功能有长期而深远的影响。

Influence of Lead Caused by the Mother Rats on the Hepatic Microsomal Drug-Metabolizing Enzyme Activities in the Descendant Rats

The present paper investigated the alterations of hepatic microsomal drug-metabolizing enzyme activities in the descendant rats after the mother rats took in different concentrations of lead water.The results showed as follows:1.Compared with the normal 4-week-old rats no changes of P450 content,NADPH-C,ANH activities were found and the AMD,GST activities were obviously lower in the 4-week-old rats whose mother took in small-dose lead water (500 μg/L) in the pregnant stage and breast-feed stage.But when their mother took in large-dose lead water(50 mg/L) in the pregnant stage and breast-feed stage,all of the drug-metabolizing enzyme activities decreased significantly.The influence of lead on GST activity was the most serious;its activity was only 27.9% that of the normal 4-week-old descendant rats.2.All of the drug-metabolizing enzyme activities in the 8-week-old descendant rats whose mother had taken in small-dose lead water in the pregtant stage and breast-feek stage could restore to normal level,but when their mother took in large-dose lead water in the pregnant stage and breast-feek stage,the drug metabolizing enzymes of the descendant rats could not restore to normal level,and the P450 content,NADPH-C,ANH,AMD,GST activities were 78.6%,76.6%,89.2%,57.5%,64.8%that of the normal 8-week-old descendant rats respectively.When mother rats went on taking in small-dose lead water,no influence on the drug-metabolizing enzymes of the descendant rats was found.But when mother rats took in large-dose lead water,the drug-metabolizing enaymes of the descendant rats were seriously inhibited and could not be restored 8 weeks after birth.Among the 5 drug-metabolizing enzymes,the influcnce of load on AMD,GST activity of the descendant rats was serious and long-lasting.From these results we can see that the influence of leed on the hepatic drug-metabolizing enzyme activities involves the choice of substrates,and the influence of lead caused by mother on the descendant is long-lasting.