摘要
目的探讨铅暴露对小鼠大脑皮质中铜水平、铜转运蛋白表达和氧化应激的影响。方法选择无特定病原体级成年雄性C57BL/6小鼠随机分为对照组、低铅暴露组和高铅暴露组,每组10只。低、高铅暴露组小鼠每天分别予饮用质量浓度为250和500 mg/L的醋酸铅饮用水,对照组小鼠饮用双蒸水,共12周。染毒结束24 h后,采用Morris水迷宫和高架十字迷宫实验检测小鼠神经行为功能;分离小鼠大脑皮质,采用电感耦合等离子-质谱法检测铅和铜水平,组织化学法检测谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性和丙二醛(MDA)水平,蛋白质印迹法检测铜转运蛋白细胞色素C氧化酶合成物(SCO)1、SCO2、细胞色素C氧化酶组装蛋白11(COX11)的表达。结果与对照组比较,低、高铅暴露组小鼠逃避潜伏期均延长(P值均<0.05),穿台次数、开臂进入次数百分比和开臂滞留时间百分比均降低(P值均<0.05)。与对照组比较,低、高铅暴露组小鼠大脑皮质中铅和铜水平均增加(P值均<0.05),GSH-Px和CAT活力均降低(P值均<0.05),SCO1相对表达水平均增加(P值均<0.05)。与低铅暴露组小鼠比较,高铅暴露组小鼠逃避潜伏期延长(P<0.05),大脑皮质中GSH-Px和CAT活力均降低(P值均<0.05),MDA水平和SCO1、SCO2相对表达水平均增加(P值均<0.05)。结论铅暴露可导致小鼠大脑皮质中铜水平与铜转运相关蛋白的表达量增加,诱导氧化应激导致中枢神经系统损伤,从而导致小鼠神经行为异常。
Objective To explore the effects of lead exposure on copper level,copper transporter protein expression and oxidative stress in mouse cerebral cortex.Methods The specific pathogen free adult male C57BL/6 mice were randomly divided into control group,low-lead exposure group and high-lead exposure group with 10 mice in each group.The mice in lowand high-lead exposure groups were respectively given 250 and 500 mg/L lead acetate in drinking water every day,and the mice in the control group were given double distilled water for 12 weeks.Twenty-four hours after exposure,Morris water maze and elevated cross maze were used to test the neurobehavioral function of mice.The cerebral cortex of mice was isolated,and the levels of lead and copper were detected by inductively coupled plasma mass spectrometry.The activities of glutathione peroxidase(GSH-Px),catalase(CAT)and malondialdehyde(MDA)were detected by histochemical method.The relative expression levels of copper transporter such as synthesis of cytochrome C oxidase(SCO)1,SCO 2,and cytochrome C oxidase assembly protein 11(COX11)were detected by western blot.Results The escape latencies of mice in the low-and high-lead exposure groups were prolonged(all P<0.05),while the number of crossing the platform,the percentage of open-arm entry times and the percentage of open-arm retention time decreased(all P<0.05)compared with the control group.Mice in both the low-and high-lead exposure groups increased levels of lead and copper in the cerebral cortex(all P<0.05),decreased GSH-Px and CAT activity(all P<0.05),and increased SCO1 relative expression(all P<0.05)compared with the control group.Mice in the high-lead exposure group showed prolonged escape latency(P<0.05),reduced GSH-Px and CAT activities in the cerebral cortex(all P<0.05),increased MDA level and relative expression of SCO1 and SCO2(all P<0.05)compared to mice in the lowlead exposure group.Conclusion Lead exposure increased the expression of copper and copper transport-related proteins in mouse cerebral cortex and induced oxidative stress leading to central nervous system damage,resulting in neurobehavioral abnormalities in mice.
作者
张学彦
李爽
吴桐
郑刚
王伟轩
张艳淑
ZHANG Xue-yan;LI Shuang;WU Tong;ZHENG Gang;WANG Wei-xuan;ZHANG Yan-shu(School of Public Health,North China University of Science and Technology,Tangshan,Hebei 063210,China;不详)
出处
《中国职业医学》
CAS
北大核心
2022年第4期368-373,共6页
China Occupational Medicine
基金
国家自然科学基金(81920108030,81773378)
关键词
铅
铜
铜转运蛋白
氧化应激
皮质
神经行为
小鼠
Lead
Copper
Copper transporter protein
Oxidative stress
Cortex
Neurobehavior
Mouse
