中文摘要：

目的 探讨不同剂量铅染毒后对大鼠脑组织和血清中铜含量以及脉络丛中铜转运蛋白表达的影响,为铅的神经毒性机制研究提供理论依据.方法 SPF级SD大鼠60只,随机分为对照组和3个铅染毒组,每组8只.铅染毒组大鼠摄入含有0、500、1 000、2000 mg/L醋酸铅饮用水8周,对照组给予2 000 mg/L醋酸钠饮水.用ICP-MS进行海马、血清、皮质、脉络丛、骨骼和脑脊液中铅、铜含量检测;用激光共聚焦和real-time PCR的方法进行铜转运蛋白Ctr1、ATX1和ATP7A的mRNA表达进行检测.结果 与对照组比较,各染毒组大鼠血清、皮质、海马、脑脊液、脉络丛和骨骼中铅含量明显升高,差异有统计学意义（P＜0.05）;各染毒组大鼠血清总铜、脑脊液、脉络丛和海马中铜的含量明显高于对照组,差异有统计学意义（P＜0.05）.激光共聚焦结果显示,对照组Ctr1表达在脉络丛的细胞质和细胞膜,铅暴露后脉络丛中Ctr1可移动到CSF面的微绒毛上.随着铅染毒剂量的增加,Ctr1的荧光强度逐渐增强,而2000 mg/L染毒组大鼠脉络丛中Ctr1的荧光强度低于1 000 mg/L染毒组.1 000和2 000 mg/L染毒组脉络丛中ATX1的荧光强度比对照组有所降低.Real-time PCR结果显示,各染毒组Ctr1、ATP7A mRNA表达均明显高于对照组,差异有统计学意义（P＜0.05）.结论 铅染毒可影响脉络丛中的铜稳态的调控,引起脑组织中铜稳态失调,这可能是铅致神经损伤的机制之一.

英文摘要：

Objective To investigate the effects of lead exposure on the copper concentration in the brain and serum and the expression of copper transporters in the choroid plexus among rats.Methods Sixty specific pathogen-free Sprague-Dawley rats were randomly divided into a control group and three lead-exposed groups,with 8 mice in each group.The lead-exposed groups were orally administrated with 500 （low-dose group）,1 000 （middle-dose group）,and 2 000 mg/L （high-dose group） lead acetate in drinking water for eight weeks.And the rats in control group were given 2 000 mg/L sodium acetate in drinking water.The content of lead and copper in the serum,hippocampus,cortex,choroid plexus,bones,and cerebrospinal fluid （CSF） was determined by inductively coupled plasma-mass spectrometry （ICP-MS）.Confocal and real-time PCR methods were applied to measure the expression of copper transporters including copper transporter 1 （Ctr1）,antioxidant protein 1 （ATX1）,and Cu ATPase （ATP7A）.Results Compared with the control group,the lead-exposed groups showed significantly higher lead concentrations in the serum,cortex,hippocampus,choroid plexus,CSF,and bones （P＜0.05） and significantly higher copper concentrations in the CSF,choroid plexus,serum,and hippocampus （P＜0.05）.Confocal images showed that Ctr1 protein was expressed in the cytoplasm and cell membrane of choroid plexus in control group.However,Ctr1 migrated to CSF surface microvilli after lead exposure.Ctr1 fluorescence intensity gradually increased with increasing dose of lead,except that the middledose group had a higher Ctr1 fluorescence intensity than the high-dose group.In addition,the middle-and highdose groups showed a lower ATX1 fluorescence intensity compared with the control group.Real-time PCR data indicated that the three lead-exposed groups showed significantly higher mRNA levels of Ctr1 and ATP7A compared with the control group （P＜0.05）.Conclusion Copper homeostasis in the choroid plexus is affected by lead exposure to ind