孕哺期铅暴露对仔鼠学习记忆能力及海马组织中P-JNK表达的影响

Effects of maternal lead exposure on learning and memory and the expression of phosphorylated c-Jun N-terminal kinase in mice offspring

目的:研究孕哺期铅暴露对仔鼠学习记忆能力及海马组织中磷酸化JNK蛋白(P-JNK)表达的影响。方法:0.3(低剂量铅暴露)、1.0(中剂量铅暴露)和3.0(高剂量铅暴露)g/L醋酸铅溶液以自由饮水方式对母鼠孕哺期染毒,每组10只,并设未染毒对照组。每组取10只仔鼠用于实验,仔鼠出生第21天用水迷宫实验检测其学习记忆能力,并检测其血液和海马组织中铅的含量,采用Western Blot法测定其海马组织中P-JNK蛋白的表达水平。结果:迷宫实验中,各组仔鼠错误次数和平均逃避潜伏期时间比较,差异有统计学意义(F=302.475和26.902,P<0.001);组间两两比较,差异均有统计学意义(P<0.05)。各组仔鼠血及海马组织铅水平比较,差异有统计学意义(F=53.139和9.392,P=0.003和0.001),组间两两比较,差异均有统计学意义(P<0.05)。各组仔鼠海马组织中P-JNK蛋白表达比较,差异有统计学意义(F=67.103,P<0.001),各剂量铅暴露组P-JNK蛋白的表达明显高于对照组(P<0.05)。结论:铅经血脑屏障,可能通过上调海马中JNK磷酸化水平并激活其信号传导通路,造成子代神经系统的损伤,从而影响学习记忆功能。

Aim：To study the effects of lead exposure during mice pregnancy on learning and memory and the expression of c-Jun N-terminal kinase phosphorylation（P-JNK） in hippocampus of their offspring.Methods：Lead exposure was conducted through freely drinking the corresponding lead acetate solutions with dosages of 0.3 g/L（low dose lead exposure）,1.0 g/L（mid dose lead exposure） and 3.0 g/L（high dose lead exposure）,respectively.The control group was not treated.Each group was composed of 10 pregnant mice.On the 21st day after birth,the ability of learning and memory of the offspring mice was detected by the morris maze test,the lead contents in blood and hippocampus were determined,and the expression of P-JNK protein in hippocampus of all the offspring was detected by Western Blot.Results：In morris maze experiment,the number of errors and the escape latent time among the 4 groups had significant differences,which were increased in the lead exposure groups（F=302.475 and 26.902,P〈0.001）.The lead levels in blood and hippocampus among the 4 groups had significant differences（F=53.139 and 9.392,P=0.003 and 0.001）,which were higher in lead exposure groups than those in the control group.The expression of P-JNK protein in hippocampus among the 4 groups had significant differences（F=67.103,P〈0.001）,which was higher in lead exposure groups than that in the control group.Conclusion：Lead can cause nervous system damage through enhancing the phosphorylation of JNK protein in hippocampus of mouse pups,which might affect learning and memory.