醋酸铅与纳米硫化铅暴露对血脑脊液屏障的屏障功能损伤的研究

来源 :中华预防医学会自由基预防医学专业委员会2015年夏季学术交流会 | 被引量 : 0次 | 上传用户:javaer0128
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  目的 探讨醋酸铅暴露与纳米硫化铅暴露后对大鼠血脑脊液屏障的屏障功能的损伤,为其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(10 mg/kg)和纳米硫化铅(nano-pbS)组(10 mg/kg),每组13 只.染毒方式为灌胃,共9 周.应用Morris 水迷宫实验测试大鼠潜伏期及穿台次数.应用透射电镜观察脉络丛上皮细胞超微结构改变.应用ELISA 试剂盒检测血清、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;应用real time-PCR 检测脉络丛ZO-1 与Occludin 的mRNA 的表达.结果 醋酸铅与纳米硫化铅暴露后,大鼠逃逸潜伏期延长、穿越平台次数下降(P<0.05),而醋酸铅组与纳米硫化铅组比较无明显差异显著(P<0.05).与对照组比较,醋酸铅与纳米硫化铅暴露后其脑脊液白蛋白及脑脊液白蛋白指数均升高(P<0.05),且纳米硫化铅组比醋酸铅组高17.65%,差异显著(P<0.05).电镜观察发现,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.激光共聚焦检荧光免疫及real time-PCR检测结果显示,醋酸铅与纳米硫化铅暴露后,大鼠脉络丛组织紧密连接蛋白ZO-1、Occludin 荧光强度均较对照组有明显减弱,mRNA 表达减少,且纳米硫化铅组比醋酸铅组更显著(P<0.05).结论 醋酸铅与纳米硫化铅暴露后可导致大鼠血脑脊液屏障的屏障功能损伤,且纳米硫化铅暴露后的部分损伤较醋酸铅严重.
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