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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 investigate the effects of lead exposure on the learning and memory abilities of offspring rats and the expression of N-methyl-D aspartate (NMDA) subunits in the hippocampus during the early stages of development. Methods Twenty-four pregnant Kunming mice of cleansing grade were randomly divided into 4 groups: control (distilled water) group and lead exposure group (0.5, 1.0 and 2.0 g / L), with 6 in each group. The rats were exposed to lead water from the first day of gestation. The offspring were weaned 21 days after birth (PND) and continued to drink lead-containing water until the end of the experiment. The learning and memory abilities of pups in PND 40 were determined by water maze. The expressions of NMDA receptor subunits (NR1, NR2A, NR2B) and m RNA in hippocampus were detected in PND10, PND20 and PND40 respectively. Results Compared with the control group, the expression levels of NR1 and NR2A protein and m RNA in the hippocampus of the lead exposure groups were lower than those in the control group, except for 0.5 g / L lead acetate exposure group of PND 10, the difference was statistically significant (P <0.05). With the increase of lead acetate exposure, the expression of NR1 and NR2A protein and m RNA in the hippocampus of neonatal rats showed a decreasing trend. Compared with the control group, the expression level of NR2B protein in hippocampus of PND 10 exposure groups and PND 20 1.0, 2.0 g / L lead exposure groups were lower than that in the control group, the difference was statistically significant (P < 0.05). However, there was no significant difference in the NR2B protein expression in the hippocampus between PND 40 exposed groups. And with the increase of lead acetate exposure, the expression level of NR2A protein in hippocampus of PND 10 and PND 20 mice showed a decreasing trend. Compared with the control group, there was no significant difference in the expression level of NR2B m RNA in hippocampus between the different doses of lead acetate exposed to different developmental stages (P> 0.05). Conclusion Lead exposure during early development can impair the learning and memory abilities of offspring and inhibit the expression of NMDA receptor subunits in the hippocampus.