Abstract: 【Objective】 Explore the effects of lead on hippocampus in central nervous tissue of developing rat. 【Methods】 A total of 48 rats(30-day old) were randomly divided into 4 groups for intragastrical perfusion of lead acetate[Pb(Ac)₂]: untreated, low[2 mg/(kg·d)], medium[20 mg/(kg·d)], and high(200 mg/kg/d) dose groups. The rats were killed six weeks post perfusion. Pb content was determined in blood by using the graphite furnace atomic absorption spectrometry. The DMT1 gene expression was analyzed in the hippocampus by RT-PCR and western blot. 【Results】 The blood lead levels in lead treatment groups were significantly higher than that of the control group(P<0.01), indicating our lead poisoning rat model was successful. No significant difference of DMT1mRNA expression; however, DMT1 protein expression increased in low dose group. In medium and high dose groups, the increase of DMT1 expression were detected in both mRNA and protein level(P<0.05 or <0.01). Our data also displayed the linear correlation between blood lead level and the expression of DMT1 gene. 【Conclusions】 The neurotoxicity induced by high blood lead level was partly mediated by over-expression of DMT1 gene in the hippocampus of central nervous system.

Key words: lead, hippocampus, DMT1, neurotoxicity

摘要： 【目的】 探索铅对发育期大鼠中枢神经神经系统海马组织的影响。 【方法】 48只健康的雄性1月龄SD大鼠,随机分为四组给予醋酸铅溶液:对照组[0 mg/(kg·d)]、低铅组[2 mg/(kg·d)]、中铅组[20 mg/(kg·d)]、高铅组[200 mg/(kg·d)],灌胃6周后处死,以石墨炉原子吸收法检测血铅,以反转录聚合酶链反应(RT-PCR)检测海马组织中二价金属转运蛋白-1(divalent metal transporter protein-1, DMT1)的mRNA表达,以免疫印迹法(western blot)检测DMT1蛋白的表达水平。 【结果】 铅处理组血铅水平均明显高于对照组(P＜0.01);铅处理组大鼠海马组织DMT1的mRNA均有表达,中、高铅组与对照组比较差异有统计学意义(P＜0.05或＜0.01);DMT1蛋白的表达水平与血铅含量呈正相关(P＜0.01)。 【结论】 铅对发育期大鼠海马组织DMT1基因及蛋白表达具有诱导作用。

关键词: 铅, 海马, 二价金属转运蛋白, 神经毒性