[Effect of lead exposure on the accumulation of copper and iron in central nervous system of rats].

Objective: To investigate the dynamic changes of copper and iron contents in brain tissue, body fluids and barriers of rats exposed to lead at different periods in order to provide a theoretical basis for the study of the mechanism of lead nerve injury. Methods: Sixty-four healthy adult SPF male SD rats were randomly divided into control group and lead exposure group, after one week of adaptive feeding, rats in the lead exposure group were treated with 250 mg/L lead acetate, and rats in control group were treated with ordinary drinking water, the experimental period was 12 weeks. After exposure for 3, 6, 9 and 12 weeks, the samples including blood, choroid plexus, cerebrospinal fluid, cortex, hippocampus, striatum, hypothalamus, amygdala, substantia nigra and cerebellum were obtained. Lead, copper and iron content in all kinds of samples were detected by Inductively Coupled Plasma Mass Spectrometry(ICP-MS). The measurement data were presented as Mean±SD, Comparison of metal contents in different tissues of rats at different time analyzed using repeated measurement analysis of variance, Two-variable correlation analysis using Spearman correlation test.The relationship between lead exposure experiod and copper and iron in samples was studied by using trend test. Results: After 12 weeks of lead exposure compared with the control group, lead contents in cortex, hippocampus, striatum, hypothalamus, amygdala, substantia nigra and cerebellum of rats were 2.21, 2.44, 2.95, 3.53, 4.01, 1.85 and 2.86 folds of control group, and the differences were statistically significant(P<0.05). At the same time, lead content in blood, cerebrospinal fluid,choroid plexus, brain microvessels and bones increased. The increase rate in the amygdala and cerebrospinal fluid ranked first among brain tissue or barrier,which were 4.01 and 3.0 folds respectively. Compared with the control group, Compared with the control group, copper content in cortex,hippocampus, striatum, hypothalamus,amygdala, cerebellum,blood,cerebrospinal fluid,choroid plexus and cerebral microvasculature showed an increasing trend among rats following 3,6,9,12 weeks of lead exposure. Copper content change in the striatum was highest among all brain tissue. The increase rate of copper content in the striatum was at the top among brain tissues. After 12 weeks of lead exposure,copper content in brain microvessels was 4.98 folds higher than that of the control group (P<0.05). After lead exposure at different periods,the iron content in the cortex, hippocampus, striatum,cerebrospinal fluid,choroid plexus and brain microvessels of experimental rats all increased(P<0.05). And the iron increase rate in the hypothalamus or cerebrospinal fluid increase ranked first among brain tissues or body fluid the most obviously. Conclusion: With the increase of exposure time, lead exposure can changes in the contents of copper and iron in different brain tissues,body fluids and barriers in rats,among which, the contents of copper and iron in the amygdala,cerebrospinal fluid and brain microvessels increase significantly. This may be related to nerve damage from lead exposure.目的： 探讨铅暴露不同时间后大鼠脑组织、体液及屏障中铜、铁含量的动态变化，以期为铅神经损伤的机制研究提供理论依据。 方法： 健康成年SPF级雄性SD大鼠64只，随机分为对照组、铅暴露组，每组32只，适应性喂养1周后，铅暴露组大鼠每天饲以250 mg/L醋酸铅饮用水，对照组大鼠每天饲以普通饮用水，实验周期12周。在染毒后第3、6、9、12周，获取全血、脉络丛、脑脊液、皮质、海马、纹状体、下丘脑、杏仁核、黑质和小脑。利用电感耦合等离子质谱仪（ICP-MS）分别检测样品中铅、铜和铁含量。分析不同染毒时间大鼠的不同组织中金属含量，验探讨铅染毒不同时间和样品中铜、铁的关系。 结果： 铅暴露12周后，与对照组比较，大鼠皮质、海马、纹状体、下丘脑、杏仁核、黑质和小脑中铅含量分别是其2.21、2.44、2.95、3.53、4.01、1.85、2.86倍，差异有统计学意义（P<0.05）；同时全血、脑脊液、脉络丛、脑微血管和骨骼中铅含量均增加；大鼠杏仁核、脑脊液中铅含量随染毒时间变化较大，分别为染毒3周的4.01和3.0倍。与对照组比较，铅暴露3、6、9、12周后，大鼠皮质、海马、纹状体、下丘脑、杏仁核、小脑、全血、脑脊液、脉络丛、脑微血管中的铜含量均呈增加趋势；脑组织中纹状体中铜含量变化较大；而铅暴露12周后，与对照组比较，脑微血管中铜含量为其4.98倍，差异有统计学意义（P<0.05）。铅暴露不同染毒时间后，大鼠皮质、海马、纹状体、脑脊液、脉络丛、脑微血管中铁含量均呈增加趋势（P< 0.05），且下丘脑中铁含量升高明显；铅染毒不同时点大鼠脑脊液中铁含量增加明显。 结论： 随着染毒时间的增加，铅暴露可致大鼠不同脑组织、体液及屏障铜和铁含量发生变化，其中，杏仁核、脑脊液、脑微血管中铜、铁含量增加明显，可能与铅暴露致神经损伤有关。.