锌对铅暴露小鼠学习记忆及海马中BDNF表达的影响

Effects of zinc on learning memory and expression of BDNF in lead exposed mice

目的观察不同剂量锌干预对铅暴露小鼠学习记忆能力和海马组织中脑源性神经营养因子(BDNF)信使RNA(mRNA)表达量的影响,研究锌对铅暴露小鼠认知损伤的干预作用及可能机制。方法60只健康小鼠随机分为空白对照组,铅暴露组和低、中、高剂量3个锌干预组,每组各12只。分别饮用双蒸水、1.0g/L醋酸铅溶液、0.2g/L醋酸锌溶液+1.0g/L醋酸铅溶液、0.4g/L醋酸锌溶液+1.0g/L醋酸铅溶液、0.6g/L醋酸锌溶液+1.0g/L醋酸铅溶液。以Morris水迷宫测定小鼠的学习记忆能力。8周后,测定血和海马中铅和锌的浓度并检测海马组织中BDNF mRNA的表达量。结果铅暴露组、低剂量锌干预组的平均逃避潜伏期高于空白对照组(P<0.01);中、高剂量锌干预组的平均逃避潜伏期低于铅暴露组和低剂量锌干预组(P<0.01),而与空白对照组比较,差异无统计学意义(P>0.05)。BDNF mRNA在铅暴露组海马中的表达量最低,空白对照组海马中的表达量最高,与锌干预剂量呈正相关,各剂量锌干预组表达量高于铅暴露组(P<0.01)。结论适量补锌可拮抗慢性铅暴露所致的血和海马中铅的含量升高及血和海马中锌的含量降低,提高海马中BDNF mRNA的表达水平,可减轻铅暴露对小鼠学习记忆能力的损伤。

Objective To investigate the protective effect of zinc in the lead exposed mice through observing the blood and hippocampal lead and zinc levels,hippocampal BDNF mRNA expression,and the spatial learning memory performance.Methods The 60 mice were equally divided into five groups,i.e.the control group,lead exposed group,low dose zinc intervention group,medium dose zinc intervention group,and high dose zinc intervention group.Under the same feeding condition,the mice were provided with distilled water,1.0 g/L lead acetate,0.2 g/L zinc acetate＋1.0 g/L lead acetate,0.4 g/L zinc acetate＋1.0 g/L lead acetate,and 0.6 g/L zinc acetate＋1.0 g/L lead acetate.Morris water maze（MWM）test was employed for evaluating the spatial learning memory ability in the mice.After eight weeks,the levels of lead and zinc in blood and hippocampus,and the hippocampal BDNF mRNA expression were determined.Results The escape latency increased in lead and low dose groups（P0.01）,while the moderate and high doses groups showed shorter escape latency than those of the lead group and low dose group（P0.01）.Compared to the control,the difference was not statistically significant（P0.05）.The expression level of hippocampal BDNF mRNA in lead exposed group was the lowest and in the control group was the highest,and also the expression was positively correlated with the doses of zinc intervention.The expression levels of hippocampal BDNF mRNA in various zinc doses intervention groups were higher than that of the lead exposed group（P0.01）.Conclusions Zinc supplement in certain amount could partially antagonize the elevation of lead and lowering of zinc in blood and hippocampal induced by lead exposure.Elevation of the expression level in hippocampal BDNF mRNA may mitigate the learning memory injury induced by lead exposure.