铅暴露对仔鼠学习记忆能力及发育早期海马组织中N-甲基-D天门冬氨酸受体亚单位表达的影响

Effects of lead exposure on learning and memory ability and expressions of NMDA receptor subunits in hippocampus of mice at early life

目的探讨铅暴露对仔鼠学习记忆能力及发育早期各阶段海马组织中N-甲基-D天门冬氨酸(NMDA)亚单位表达的影响。方法将24只清洁级妊娠昆明小鼠随机分为4组,分别为对照(蒸馏水)组及0.5、1.0、2.0 g/L铅暴露组,每组6只。采用自由饮水方式进行染毒,母鼠从妊娠第1天起开始饮用含铅水,仔鼠于出生后(PND)21天断乳,继续饮含铅水至实验结束。水迷宫测定PND 40仔鼠学习记忆能力;并分别于PND10、PND20和PND40,测定海马组织中NMDA各受体亚单位(NR1、NR2A、NR2B)蛋白和m RNA的表达水平。结果与对照组比较,各剂量乙酸铅暴露组仔鼠海马组织中NR1和NR2A蛋白及m RNA的表达水平均较低,除PND 10的0.5 g/L乙酸铅暴露组外,差异有统计学意义(P<0.05);且随着乙酸铅暴露剂量的升高,仔鼠海马组织中NR1和NR2A蛋白及m RNA的表达水平呈下降趋势。与对照组比较,PND 10时各剂量乙酸铅暴露组及PND 20时1.0、2.0 g/L乙酸铅暴露组仔鼠海马组织中NR2B蛋白的表达水平均较低,差异有统计学意义(P<0.05);而PND 40时各剂量乙酸铅暴露组仔鼠海马组织中NR2B蛋白的表达水平均无明显改变。且随着乙酸铅暴露剂量的升高,PND 10、PND 20时仔鼠海马组织中NR2A蛋白的表达水平均呈下降趋势。各剂量乙酸铅暴露不同发育阶段仔鼠海马组织中NR2B m RNA的表达水平与对照组比较,差异均无统计学意义(P>0.05)。结论发育早期铅暴露可损伤仔鼠的学习记忆能力,并且抑制仔鼠海马组织中NMDA受体各亚单位的表达。

Objective To explore the effects of lead exposure on learning and memory ability and expressions of N-methyl-Daspartate receptor（NMDA） subunits in the hippocampus of mice at the early developmental stages. Methods Twenty-four female pregnant mice were randomly divided into four groups： control（distilled water） group,0.5,1.0 and 2.0 g/L lead exposed group,six in each. The pregnant mice were given lead acetate through drinking water from the first day of gestation,pups were weaned on postnatal day（PND） 21,and still drank the same water until the end of the test. The spatial learning and memory ability of PND 40 mice was measured and the expressions of NMDA receptor（NR1, NR2 A, NR2B） subunits in the hippocampus of PND 10, 20 and 40 mice were tested. Results Compared with the control group, NR1, NR2 A protein and m RNA expression levels were lower in lead-exposed groups, except 0.5 g/L lead exposure group at PND10 significantly（P〈0.05）. With the increase of lead exposure, NR1, NR2 A protein and m RNA expression levels declined. Compared with the control group, each group of lead exposure of PND 10 and 1.0 g/L and 2.0 g/L lead exposure group at PND 20 pups hippocampus NR2 B protein expression levels were significantly lower（P〈0.05）. With the increase of lead exposure, NR2 A protein expression levels declined at PND 10, 20, and no significant difference was seen in NR2 B m RNA expression levels at different development stages. Conclusion Lead exposure at the early life may cause deficits in learning and memory ability and inhibit the expressions of NMDA receptor subunits.