铅神经毒作用研究
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摘要
铅化合物应用广泛,长期低水平铅暴露可对人体中枢神经系统造成损害,严重者出现中毒性脑病。铅对中枢神经系统的作用机制主要表现在以下几个方面:对血脑屏障的损伤、影响神经胶质细胞的正常功能、诱导神经细胞凋亡、引起脂质过氧化损伤、干扰神经递质的储存和释放等。近年来,人们对铅神经毒作用又有了新的认识,本文就此做一综述。
Lead compounds have been widely used and long-term low levels of lead exposure are harmful to the central nervous system,even appear to toxic encephalopathy. Lead on the central nervous system to be displayed in the following aspects: damage the blood-brain barrier,affect the normal function of glial cells,induced apoptosis of nerve cells,cause lipid peroxidation damage and influence the neurotransmitter storage and release and so on. In recent years,people has been a new understanding of neurotoxic effects of lead. This article reviews the neurotoxic effects of lead.
Lead compounds have been widely used and long-term low levels of lead exposure are harmful to the central nervous system,even appear to toxic encephalopathy. Lead on the central nervous system to be displayed in the following aspects: damage the blood-brain barrier,affect the normal function of glial cells,induced apoptosis of nerve cells,cause lipid peroxidation damage and influence the neurotransmitter storage and release and so on. In recent years,people has been a new understanding of neurotoxic effects of lead. This article reviews the neurotoxic effects of lead.
引文
[1]Laidlaw M A S,Mohmmad S M,Gulson B L,et al.Estimates of potential childhood lead exposure from contaminated soil using the US EPA IEUBK Model in Sydney,Australia[J].Environmental Research,2017,156:781-790.
[2]韩松,梁多宏,张莹,等.宫内低水平铅暴露对新生儿神经行为及体格发育影响[J].中国公共卫生,2013,29(9):1283-1285.
[3]Tietz S,Engelhardt B.Brain barriers:crosstalk between complex tight junctions and adherens junctions[J].J Cell Biol,2015,209(4):493-506.
[4]Skerfving S,L9fmark L,Lundh T,et al.Late effects of low blood lead concentrations in children on school performance and cognitive functions[J].Neurotoxicology,2015,49:114-120.
[5]Luo W,Ruan D,Yan C,et al.Effects of chronic lead exposure on functions of nervous system in Chinese children and developmental rats[J].Neurotoxicology,2012,33(4):862-871.
[6]Sánchez-Martín F J,Fan Y,Lindquist D M,et al.Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells[J].Plos One,2013,8(11):e80558.
[7]Pascual O,Achour S B,Rostaing P,et al.Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission[J].Proceedings of the National Academy of Sciences,2012,109(4):197-205.
[8]Kumawat K L,Kaushik D K,Goswami P,et al.Acute exposure to lead acetate activates microglia and induces subsequent bystander neuronal death via caspase-3 activation[J].Neurotoxicology,2014,41:143-153.
[9]Guan R,Wang T,Chen J,et al.The activation of microglia caused by lead and manganese co-exposure induces activation of astrocytes and decrease of glutamine synthetaseactivity[J].Chinese Journal of Cellular and Molecular Immunology,2016,32(3):313-318.
[10]Liu J T,Dong M H,Zhang J Q,et al.Microglia and astroglia:the role of neuroinflammation in lead toxicity and neuronal injury in the brain[J].Neuroimmunology and Neuroinflammation,2015,2(3):131.
[11]Wei J,Du K,Cai Q,et al.Lead induces COX-2 expression in glial cells in a NFAT-dependent,AP-1/NFκB-independent manner[J].Toxicology,2014,325:67-73.
[12]Müller Y M R,Kobus K,Schatz J C,et al.Prenatal lead acetate exposure induces apoptosis and changes GFAP expression during spinal cord development[J].Ecotoxicology and Environmental Safety,2012,75:223-229.
[13]Moshtaghie M,Malekpouri P,Saeed-zadeh M,et al.Catecholamine contents of different region of adult rat brain are altered following short and long-term exposures to Pb2+[J].Iranian Journal of Pharmaceutical Research,2013,12(2):461.
[14]De Almeida Lopes A C B,Navas-Acien A,Zamoiski R,et al.Risk factors for lead exposure in adult population in southern Brazil[J].Journal of Toxicology and Environmental Health,2015,78(2):92-108.
[15]Ahlberg S,Antonopulos A,Diendorf J,et al.PVP-coated,negatively charged silver nanoparticles:A multi-center study of their physicochemical characteristics,cell culture and in vivo experiments[J].Beilstein Journal of Nanotechnology,2014,5:1944.
[16]Robinson S R,Lee A,Bishop G M,et al.Inhibition of astrocytic glutamine synthetase by lead is associated with a slowed clearance of hydrogen peroxide by the glutathione system[J].Frontiers in Integrative Neuroscience,2015,9:61.
[17]Sharifi A M,Mousavi S H,Jorjani M.Effect of chronic lead exposure on pro-apoptotic Bax and anti-apoptotic Bcl-2 protein expression in rat hippocampus in vivo[J].Cellular and Molecular Neurobiology,2010,30(5):769-774.
[18]Dou C,Zhang J.Effects of lead on neurogenesis during zebrafish embryonic brain development[J].Journal of Hazardous Materials,2011,194:277-282.
[19]Baranowska-Bosiacka I,Stru6)zyńska L,Gutowska I,et al.Perinatal exposure to lead induces morphological,ultrastructural and molecular alterations in the hippocampus[J].Toxicology,2013,303:187-200.
[20]Chan Y H,Gao M,Wu W.Are newborn rat-derived neural stem cells more sensitive to lead neurotoxicity?[J].Neural Regeneration Research,2013,8(7):581.
[21]何胜男,秦文霞,卢艳红,等.对氨基水杨酸钠对铅诱导体外培养PC12细胞凋亡的影响[J].中国药理学与毒理学杂志,2017,30(2):159-164.
[22]Engstrom A,Wang H,Xia Z.Lead decreases cell survival,proliferation,and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases[J].Toxicology in Vitro,2015,29(5):1146-1155.
[23]Mousa A M,Al-Fadhli A S,Rao M S,et al.Gestational lead exposure induces developmental abnormalities and upregulates apoptosis of fetal cerebellar cells in rats[J].Drug and Chemical Toxicology,2015,38(1):73-83.
[24]邓祥发,区仕燕,姜岳明,等.对氨基水杨酸钠对亚慢性铅暴露大鼠海马超微结构的影响[J].毒理学杂志,2009,23(3):213-216.
[25]Sim7es M R,Aguado A,Fiorim J,et al.MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways[J].Toxicology and Applied Pharmacology,2015,283(2):127-138.
[26]Corsetti G,Romano C,Stacchiotti A,et al.Endoplasmic reticulum stress and apoptosis triggered by sub-chronic lead exposure in mice spleen:a histopathologicalstudy[J].Biological Trace Element Research,2017,178(1):86-97.
[27]Boulle F,Van Den Hove D L A,Jakob S B,et al.Epigenetic regulation of the BDNF gene:implications for psychiatric disorders[J].Molecular Psychiatry,2012,17(6):584.
[28]Neal A P,Worley P F,Guilarte T R.Lead exposure during synaptogenesis alters NMDA receptor targeting via NMDA receptor inhibition[J].Neurotoxicology,2011,32(2):281-289.
[29]Senut M C,Sen A,Cingolani P,et al.Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation[J].Toxicological Sciences,2014,139(1):142-161.
[30]Hanna C W,Bloom M S,Robinson W P,et al.DNA methylation changes in whole blood is associated with exposure to the environmental contaminants,mercury,lead,cadmium and bisphenol A,in women undergoing ovarian stimulation for IVF[J].Human Reproduction,2012,27(5):1401-1410.
[31]Schneider J S,Kidd S K,Anderson D W.Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus[J].Toxicology Letters,2013,217(1):75-81.
[32]康蓓佩,赵芳,苏鹏,等.XIAP蛋白表达改变在铅诱导小鼠海马神经元细胞损伤中的作用[J].实用预防医学,2015,22(5):513-516.
[33]Guo S,Zhou J,Chen X,et al.Bystander effects of PC12 cells treated with Pb2+depend on ROS-mitochondria-dependent apoptotic signaling via gap-junctional intercellular communication[J].Toxicology Letters,2014,229(1):150-157.
[34]Han Y,Li C,Su M,et al.Antagonistic effects of selenium on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens[J].Oncotarget,2017,8(20):33725.
[35]Lopes A C,Peixe T S,Mesas A E,et al.Lead exposure and oxidative stress:a systematic review[J].Reviews of Environmental Contamination and Toxicology.2016,236:193-238.
[36]Zyk J,Ostalowska A,Zalejska,et al.Beta-carotene reduces oxidative stress,improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers[J].Toxicology and Applied Pharmacology,2014,280(1):36
[37]Li X,Ye F,Li L,et al.The role of HO-1 in protection against lead-induced neurotoxicity[J].Neurotoxicology,2016,52:1-11.
[38]Abdella E M,El-Sisy S F,El-Dash H A.Neurobehavioral and neuropathological studies of the protective effects of alpha lipoic acid(α-LA)against lead toxicity in rats[J].Original Research,2016,6(1):43-51.
[39]Li N,Liu X,Zhang P,et al.The effects of early life lead exposure on the expression of interleukin(IL)1β,IL-6,and glial fibrillary acidic protein in the hippocampus of mouse pups[J].Human&Experimental Toxicology,2015,34(4):357-363.
[40]Karamian R,Komaki A,Salehi I,et al.Vitamin C reserves lead-induced deficits in hippocampalsynaptic Plasticity in rats[J].Brain Research Bulletin,2015,116:7-15.
[41]Guariglia S R,Stansfield K H,Mc Glothan J,et al.Chronic early life lead(Pb2+)exposure alters presynaptic vesicle pools in hippocampal synapses[J].BMC Pharmacology and Toxicology,2016,17(1):56.
[42]Neal A P,Stansfield K H,Worley P F,et al.Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release:potential role of NMDA receptor-dependent BDNF signaling[J].Toxicological Sciences,2010,116(1):249-263.
[43]Wang X M,Liu W J,Zhang R,et al.Effects of exposure to low-level lead on spatial learning and memory and the expression of m GluR1,NMDA receptor in different developmental stages of rats[J].Toxicology and Industrial Health,2013,29(8):686-696.
[44]罗旖旎,李勇,彭东杰,等.PAS-Na对铅致幼龄大鼠学习记忆及氨基酸类神经递质含量的影响[J].毒理学杂志,2016,30(6):444-447.
[45]田凯琦,翟福骏,吴京泽,等.纳米硫化铅和醋酸铅对大鼠脑组织氨基酸类神经递质影响研究[J].中国职业医学,2015,42(5):500-504.
[2]韩松,梁多宏,张莹,等.宫内低水平铅暴露对新生儿神经行为及体格发育影响[J].中国公共卫生,2013,29(9):1283-1285.
[3]Tietz S,Engelhardt B.Brain barriers:crosstalk between complex tight junctions and adherens junctions[J].J Cell Biol,2015,209(4):493-506.
[4]Skerfving S,L9fmark L,Lundh T,et al.Late effects of low blood lead concentrations in children on school performance and cognitive functions[J].Neurotoxicology,2015,49:114-120.
[5]Luo W,Ruan D,Yan C,et al.Effects of chronic lead exposure on functions of nervous system in Chinese children and developmental rats[J].Neurotoxicology,2012,33(4):862-871.
[6]Sánchez-Martín F J,Fan Y,Lindquist D M,et al.Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells[J].Plos One,2013,8(11):e80558.
[7]Pascual O,Achour S B,Rostaing P,et al.Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission[J].Proceedings of the National Academy of Sciences,2012,109(4):197-205.
[8]Kumawat K L,Kaushik D K,Goswami P,et al.Acute exposure to lead acetate activates microglia and induces subsequent bystander neuronal death via caspase-3 activation[J].Neurotoxicology,2014,41:143-153.
[9]Guan R,Wang T,Chen J,et al.The activation of microglia caused by lead and manganese co-exposure induces activation of astrocytes and decrease of glutamine synthetaseactivity[J].Chinese Journal of Cellular and Molecular Immunology,2016,32(3):313-318.
[10]Liu J T,Dong M H,Zhang J Q,et al.Microglia and astroglia:the role of neuroinflammation in lead toxicity and neuronal injury in the brain[J].Neuroimmunology and Neuroinflammation,2015,2(3):131.
[11]Wei J,Du K,Cai Q,et al.Lead induces COX-2 expression in glial cells in a NFAT-dependent,AP-1/NFκB-independent manner[J].Toxicology,2014,325:67-73.
[12]Müller Y M R,Kobus K,Schatz J C,et al.Prenatal lead acetate exposure induces apoptosis and changes GFAP expression during spinal cord development[J].Ecotoxicology and Environmental Safety,2012,75:223-229.
[13]Moshtaghie M,Malekpouri P,Saeed-zadeh M,et al.Catecholamine contents of different region of adult rat brain are altered following short and long-term exposures to Pb2+[J].Iranian Journal of Pharmaceutical Research,2013,12(2):461.
[14]De Almeida Lopes A C B,Navas-Acien A,Zamoiski R,et al.Risk factors for lead exposure in adult population in southern Brazil[J].Journal of Toxicology and Environmental Health,2015,78(2):92-108.
[15]Ahlberg S,Antonopulos A,Diendorf J,et al.PVP-coated,negatively charged silver nanoparticles:A multi-center study of their physicochemical characteristics,cell culture and in vivo experiments[J].Beilstein Journal of Nanotechnology,2014,5:1944.
[16]Robinson S R,Lee A,Bishop G M,et al.Inhibition of astrocytic glutamine synthetase by lead is associated with a slowed clearance of hydrogen peroxide by the glutathione system[J].Frontiers in Integrative Neuroscience,2015,9:61.
[17]Sharifi A M,Mousavi S H,Jorjani M.Effect of chronic lead exposure on pro-apoptotic Bax and anti-apoptotic Bcl-2 protein expression in rat hippocampus in vivo[J].Cellular and Molecular Neurobiology,2010,30(5):769-774.
[18]Dou C,Zhang J.Effects of lead on neurogenesis during zebrafish embryonic brain development[J].Journal of Hazardous Materials,2011,194:277-282.
[19]Baranowska-Bosiacka I,Stru6)zyńska L,Gutowska I,et al.Perinatal exposure to lead induces morphological,ultrastructural and molecular alterations in the hippocampus[J].Toxicology,2013,303:187-200.
[20]Chan Y H,Gao M,Wu W.Are newborn rat-derived neural stem cells more sensitive to lead neurotoxicity?[J].Neural Regeneration Research,2013,8(7):581.
[21]何胜男,秦文霞,卢艳红,等.对氨基水杨酸钠对铅诱导体外培养PC12细胞凋亡的影响[J].中国药理学与毒理学杂志,2017,30(2):159-164.
[22]Engstrom A,Wang H,Xia Z.Lead decreases cell survival,proliferation,and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases[J].Toxicology in Vitro,2015,29(5):1146-1155.
[23]Mousa A M,Al-Fadhli A S,Rao M S,et al.Gestational lead exposure induces developmental abnormalities and upregulates apoptosis of fetal cerebellar cells in rats[J].Drug and Chemical Toxicology,2015,38(1):73-83.
[24]邓祥发,区仕燕,姜岳明,等.对氨基水杨酸钠对亚慢性铅暴露大鼠海马超微结构的影响[J].毒理学杂志,2009,23(3):213-216.
[25]Sim7es M R,Aguado A,Fiorim J,et al.MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways[J].Toxicology and Applied Pharmacology,2015,283(2):127-138.
[26]Corsetti G,Romano C,Stacchiotti A,et al.Endoplasmic reticulum stress and apoptosis triggered by sub-chronic lead exposure in mice spleen:a histopathologicalstudy[J].Biological Trace Element Research,2017,178(1):86-97.
[27]Boulle F,Van Den Hove D L A,Jakob S B,et al.Epigenetic regulation of the BDNF gene:implications for psychiatric disorders[J].Molecular Psychiatry,2012,17(6):584.
[28]Neal A P,Worley P F,Guilarte T R.Lead exposure during synaptogenesis alters NMDA receptor targeting via NMDA receptor inhibition[J].Neurotoxicology,2011,32(2):281-289.
[29]Senut M C,Sen A,Cingolani P,et al.Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation[J].Toxicological Sciences,2014,139(1):142-161.
[30]Hanna C W,Bloom M S,Robinson W P,et al.DNA methylation changes in whole blood is associated with exposure to the environmental contaminants,mercury,lead,cadmium and bisphenol A,in women undergoing ovarian stimulation for IVF[J].Human Reproduction,2012,27(5):1401-1410.
[31]Schneider J S,Kidd S K,Anderson D W.Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus[J].Toxicology Letters,2013,217(1):75-81.
[32]康蓓佩,赵芳,苏鹏,等.XIAP蛋白表达改变在铅诱导小鼠海马神经元细胞损伤中的作用[J].实用预防医学,2015,22(5):513-516.
[33]Guo S,Zhou J,Chen X,et al.Bystander effects of PC12 cells treated with Pb2+depend on ROS-mitochondria-dependent apoptotic signaling via gap-junctional intercellular communication[J].Toxicology Letters,2014,229(1):150-157.
[34]Han Y,Li C,Su M,et al.Antagonistic effects of selenium on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens[J].Oncotarget,2017,8(20):33725.
[35]Lopes A C,Peixe T S,Mesas A E,et al.Lead exposure and oxidative stress:a systematic review[J].Reviews of Environmental Contamination and Toxicology.2016,236:193-238.
[36]Zyk J,Ostalowska A,Zalejska,et al.Beta-carotene reduces oxidative stress,improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers[J].Toxicology and Applied Pharmacology,2014,280(1):36
[37]Li X,Ye F,Li L,et al.The role of HO-1 in protection against lead-induced neurotoxicity[J].Neurotoxicology,2016,52:1-11.
[38]Abdella E M,El-Sisy S F,El-Dash H A.Neurobehavioral and neuropathological studies of the protective effects of alpha lipoic acid(α-LA)against lead toxicity in rats[J].Original Research,2016,6(1):43-51.
[39]Li N,Liu X,Zhang P,et al.The effects of early life lead exposure on the expression of interleukin(IL)1β,IL-6,and glial fibrillary acidic protein in the hippocampus of mouse pups[J].Human&Experimental Toxicology,2015,34(4):357-363.
[40]Karamian R,Komaki A,Salehi I,et al.Vitamin C reserves lead-induced deficits in hippocampalsynaptic Plasticity in rats[J].Brain Research Bulletin,2015,116:7-15.
[41]Guariglia S R,Stansfield K H,Mc Glothan J,et al.Chronic early life lead(Pb2+)exposure alters presynaptic vesicle pools in hippocampal synapses[J].BMC Pharmacology and Toxicology,2016,17(1):56.
[42]Neal A P,Stansfield K H,Worley P F,et al.Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release:potential role of NMDA receptor-dependent BDNF signaling[J].Toxicological Sciences,2010,116(1):249-263.
[43]Wang X M,Liu W J,Zhang R,et al.Effects of exposure to low-level lead on spatial learning and memory and the expression of m GluR1,NMDA receptor in different developmental stages of rats[J].Toxicology and Industrial Health,2013,29(8):686-696.
[44]罗旖旎,李勇,彭东杰,等.PAS-Na对铅致幼龄大鼠学习记忆及氨基酸类神经递质含量的影响[J].毒理学杂志,2016,30(6):444-447.
[45]田凯琦,翟福骏,吴京泽,等.纳米硫化铅和醋酸铅对大鼠脑组织氨基酸类神经递质影响研究[J].中国职业医学,2015,42(5):500-504.