中文摘要：

目的探讨醋酸铅与纳米硫化铅染毒对大鼠血脑脊液屏障的屏障功能的损伤，为铅中毒防治提供理论依据。方法39只SPF级SD雄性大鼠随机分为对照组、醋酸铅组（20mg／kg）和纳米硫化铅组（20mg／kg），每组13只。灌胃染毒，每天1次，每周染5d．，共9周。用Morris水迷宫测试大鼠学习和记忆功能；应用ELISA方法检测血清、脑脊液中白蛋白含量水平，并计算脑脊液白蛋白指数；激光共聚焦荧光免疫方法检测脉络丛胞质附着蛋白-1（ZO-1）及闭合蛋白（Occludin）表达分布，实时定量荧光PCR检测脉络丛ZO-1与Occludin的mRNA的表达，透射电镜观察脉络丛上皮细胞趟微结构的改变。结果与对照组比较，醋酸铅与纳米硫化铅组大鼠的逃逸潜伏期均延长、穿越平台次数均下降，差异有统计学意义（P〈0．05）；与对照组比较，醋酸铅和纳米硫化铅组大鼠脑脊液中白蛋白含量及白蛋白指数增加；脉络丛中ZO-1、Occludin荧光强度及mRNA相对表达量降低，差异均有统计学意义（P〈0．05）。与醋酸铅组比较，纳米硫化铅组脑脊液中白蛋白含量、脑脊液白蛋白指数升高；脉络丛组织紧密连接蛋白ZO—1、Occludin荧光强度及mRNA相对表达量均降低，差异均有统计学意义（P〈0．05）。电子显微镜观察显示，醋酸铅与纳米硫化铅染毒均导致脉络丛上皮细胞微绒毛结构紊乱、缩短；线粒体结构出现空泡，细胞间连接部分断裂等。结论醋酸铅与纳米硫化铅染毒可导致大鼠血脑脊液屏障的屏障功能损伤，且纳米硫化铅染毒后的部分损伤较醋酸铅严重。

英文摘要：

Objective To investigate the damage of hlood-cerebrospinal fluid barrier （BCB） of rats induced by lead and nano-lead exposure in order to provide the basis for mechanism study of lead neurotoxicity. Methods 39 male rats were randomly divided into control group, lead acetate exposed group and nano-lead exposed group. Rats in lead acetate exposed group and nano-lead exposed group were given 20 mg/kg lead acetate or nano-lead by oral gavage and rats in control groups were given the same amount saline for 9 weeks. Morris maze was used to test the learning iunction, serum albumin and CSF alhumin were determined by ELISA. Confocal laser scanning microscope was applied to detect ZO-1 and Oecludin protein expression in ehoroid plexus, real time-PCR was used to test the expression of ZO-1 and Occludin mRNA expression. Pathological changes of ehoroid plexus cells were observed by the eleetron microscopy. Results Compared with the control group, the escape latency of rats in lead acetate or nano-lead exposure group were longer and times of across platform were less. The levels of CSF alhumin and the CSF alhumin index in lead acetate or nano-lead exposed rats were obviously higher, and the fluorescence intensity of ZO-I, Occludin as well as mRNA expressions were lower than those in control group（P〈0.05）. Compared with lead acetate exposed group, the levels of CSF albumin and the CSF albumin index in nano-lead exposure group were higher. The fluorescence intensity and mRNA expressions of ZO-1, Oeeludin in nano-lead exposure group were than those in lead acetate group （P〈0.05）. Electron microscopy revealed that lead acetate or nano-lead exposure could induee shorter microvillus of choroid plexus epithelial cells, mitochondrion destruction and partial disconnection in intracellular junctions between two adjacent epithelial cells. Conclusion Lead acetate and nano-lead exposed can result in the blood-eerebrospinal fluid barrier damage, whieh may involve in the process of lead induced neurotoxicity. Meanwhile, nan