铝的神经毒性与神经退行性变

牛侨

doi:10.12405/j.issn.2097-1486.2022.01.010

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铝的神经毒性与神经退行性变

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- 铝的神经毒性与神经退行性变
- Study on the neurotoxicity and neurodegeneration of Aluminum
- 新兴科学和技术趋势 2022年1卷第1期页码：97-106
- 作者机构：
  
  山西医科大学　公共卫生学院，山西　太原　030001
- 作者简介：
  
  [ "牛侨，男，教授；博士，博士生导师；国务院特贴专家，山西省教学名师，山西省优秀研究生指导教师；担任中国环境诱变剂学会理事，环境与神经退行性疾病专业委员会主任，中国毒理学会常务理事，神经毒理专业委员会副主任，《European Journal of Inflammation》等学术期刊编委；目前主要从事化学物的神经毒性方面的理论研究工作；主持完成国家和省部级项目20余项，包括国家自然科学基金重点项目、面上项目、教育部博士点基金、山西省自然科学基金等；在Neurotoxicology，Neurotoxicity Research，Chemosphere等期刊发表论文370余篇（其中SCI收录115篇），获得国家发明专利5项，主编英文专著1部、中文专著1部，主编参编规划教材13部；曾获“中华预防医学会公共卫生与预防医学发展贡献奖”“中国毒理学会毒理学杰出贡献奖”，山西省自然科学一等奖及中华预防医学科技二等奖。E-mail：niuqiao55@sxmu.edu.cn" ]
- 基金信息：
- DOI：10.12405/j.issn.2097-1486.2022.01.010
  中图分类号： R114
- 纸质出版日期：2022-09，
  
  收稿日期：2022-05-15，
  
  修回日期：2022-06-08，
- 稿件说明：
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牛侨.铝的神经毒性与神经退行性变[J].新兴科学和技术趋势,2022,1(1):97-106.

NIU QIAO. Study on the neurotoxicity and neurodegeneration of Aluminum. [J]. Emerging Science and Technology, 2022,1(1):97-106.
牛侨.铝的神经毒性与神经退行性变[J].新兴科学和技术趋势,2022,1(1):97-106. DOI： 10.12405/j.issn.2097-1486.2022.01.010.

NIU QIAO. Study on the neurotoxicity and neurodegeneration of Aluminum. [J]. Emerging Science and Technology, 2022,1(1):97-106. DOI： 10.12405/j.issn.2097-1486.2022.01.010.

摘要

铝是神经毒元素，可通过各种途径进入体内，能通过血脑屏障，甚至直接通过嗅神经进入脑组织，表现出神经毒作用，导致认知功能损害，被认为与神经退行性疾病如阿尔茨海默病、巴金森病有关，甚至是诱发阿尔茨海默病的环境因素之一。现有研究表明，铝可引起职业暴露工人神经行为和认知功能下降，脑电图和脑电地形图改变。动物实验病理改变表现为大脑皮质和海马神经细胞减少、排列紊乱，突触结构改变，线粒体、内质网破坏，神经细胞凋亡。铝的神经毒性机制包括：引起神经递质合成和传输紊乱，影响能量代谢，脂质过氧化，影响钙代谢及相关酶，引起神经细胞凋亡和非凋亡程序性死亡（包括程序性坏死和自噬），引起Tau蛋白过度磷酸化形成神经原纤维缠结，导致β-APP过度表达形成Aβ沉积，影

响Glu-NO-cGMP通路降低突触可塑性，影响线粒体和线粒体酶。铝还可和遗传因素ApoE

4协同作用，加速痴呆发生。铝还可引起表观遗传修饰改变，如改变甲基化程度而引起认知功能损害。

Abstract

Studies have shown that aluminum can cause neurobehavioral and cognitive decline

and also changes in electroencephalogram and brain electrical topography in occupationally Al-exposed workers. The pathological changes in animal experiments showed that the cortical and hippocampal neural cells reduced and disordered

synaptic structure changed

mitochondria and endoplasmic reticulum destroyed

and neural cells were apoptotic. Aluminum-induced neurotoxic mechanisms includes: to induce neurotransmitter synthesis and transmission disorder

affect energy metabolism

promote lipid peroxidation

disturb calcium metabolism and related enzymes

induce neuronal apoptosis and non-apoptotic programmed death (including necroptosis and autophagy)

cause Tau protein hyperphosphorylation to form neurofibrillary tangles

and lead toβ-APP overexpression to form Aβdeposition

affect Glu-No-CGMP pathway to decrease synaptic plasticity

impair mitochondria and mitochondrial enzymes. Aluminum can act synergistically with genetic factor ApoE ε 4 to accelerate the occurrence of dementia

and also cause epigenetic modifications

such as changes in methylation levels that can lead to cognitive impairment.

关键词

铝神经毒性认知功能损害阿尔茨海默病发病机制

Keywords

aluminumneurotoxicitycognitive impairmentAlzheimer's diseasepathogenesis

references

ELLIOTT HL, DRYBURGH F, FELL GS, et al. A-luminum toxicity during regular haemodialysis[J]. Br Med J, 1978, 1(6120): 1101-1103.

HANNINEN H, MATIKAINEN E, et al. Internal load of aluminum and the central nervous system function of aluminum welders[J]. Scand J Work Environ Health, 1994, 20(4): 279-285. doi: 10.5271/sjweh.1397http://doi.org/10.5271/sjweh.1397.

RIIHIMAKI V, HANNINEN H, AKILA R, et al. Body burden of aluminum in relation to central nervous system function among metal inert-gas welders[J]. Scand J Work Environ Health, 2000, 26(2): 118-130.

何淑嫦, 张爱民, 牛侨, 等.铝电解工神经行为、自主神经功能的改变[J].卫生研究, 2003, 32(3): 177-179.

HE SC, QIAO N, SHENG W. Neurobehavioral, autonomic nervous function and lymphocyte subsets among aluminum electrolytic workers[J]. Int J Immunopathol Pharmacol, 2003, 16(2): 139-144. doi: 10.1177/039463200301600207http://doi.org/10.1177/039463200301600207.

LU X, LIANG R, NIU Q, et al. Cognitive disorders and tau-protein expression among retired aluminum smelting workers[J]. Journal of Occupational and Environmental Medicine, 2014, 56(2): 155-60.

MENG H, WANG S, NIU Q, et al. Cognitive impairment of workers in a large-scale aluminium factory in China: a cross-sectional stud[J]. BMJ Open, 2019, 9(6): E027154.

LU XT, XU SM, NIU Q, et al. Longitudinal study of the effects of occupational aluminium exposure on workers' cognition[J]. Chemosphere, 2021, 271: 129569. doi: 10.1016/j.chemosphere.2021.129569http://doi.org/10.1016/j.chemosphere.2021.129569.

EXLEY C, VICKERS T. Elevated brain aluminium and early onset Alzheimer's disease in an individual oc-cupationally exposed to aluminium: a case report[J]. J Med Case Rep, 2014, 10(8): 41.

PERL DP. Exposure to aluminium and the subsequent development of a disorder with features of Alzheimer's disease[J]. JNeurolNeurosurgPsychiatry.2006, 77(7): 811. doi: 10.1136/jnnp.2006.090613http://doi.org/10.1136/jnnp.2006.090613.

黄国伟, 康静, 张文治, 等.铝对体外人胚大脑神经细胞毒作用的研究[J].中华预防医学杂志, 2000, 34(2): 106-10.

杨艳旭, 牛侨, 等.铝对大鼠脑组织脂质过氧化作用的影响及其性别差异[J].中华劳动卫生职业病杂志, 2006, 24(5): 281-283.

牛丕业, 何淑嫦, 牛侨.天麻对染铝大鼠胆碱能系统的影响[J].工业卫生与职业病, 2003, 29(5): 260-262.

叶建锋, 胡贵方, 高宁.氯化铝染毒后大鼠行为学和胆碱酯酶的变化[J].卫生毒理学杂, 1999, 13(3): 217.

COCHAN M, ELLIOTT DC, BRENNAN P, et al. Inhibition of protein kinase activation by low concentrations of aluminum[J]. Clin Chim Acta, 1990, 194(2-3): 167-172.

牛丕业, 牛侨, 何淑嫦.天麻对染铝大鼠大脑氨基酸递质的影响[J].环境与职业医, 2004, 21(1): 55-57.

NIU Q, NIU P, ZHANG Q, et al. The Role of Alteration of Glutamic Acid and GABA in Learning and Memory Impairment of Rats Induced By Aluminum[J]. Eur J Inflamm, 2005, 3(2): 97-101.

MANZO L, ARTIGAS F, MARTINEZ E, et al. "Biochemical markers of neurotoxicity. A review of mechanistic studies and applications"[J]. Human & Experimental Toxicology, 1996, 1(15): S20.

CURCARELLA C, MONTOLIU C, HERMENEGILDO C, et al. Chronic exposure to aluminum impairs neuronal glutamate-nitric oxide-cyclic GMP pathway[J]. J Neurochem, 1998, 70(4): 1609-1614. doi: 10.1046/j.1471-4159.1998.70041609http://doi.org/10.1046/j.1471-4159.1998.70041609.

CANALES JJ, CORBALAN R, MONTOLIN C, et al. Aluminium impairs the Glutamate-nitric oxidecGMP pathway in cultured neurons and in rat brain in vivo: molecular mechanisms and implications for neuropathology[J]. J Inorg Biochem, 2001, 87(1-2): 63-69.

唐焕文, 秦小敏, 黄彦妮, 等.染铝大鼠学习记忆功能及单胺类神经递质含量的变化[J].中国职业医学, 2002, 29(3): 17-19.

ALESSIO L, APOSTOLI P, FERIOLI A, et al. Behaviour of biological indicators of internal dose and some neuro-endocrine tests in aluminium workers[J]. Med Lav, 1989, 80(4): 290-300.

ZATTA P, NICOSIA V, ZAMBENEDETTI P. E-valuation of MAO activities on murine neuroblastoma cells upon acute or chronic treatment with aluminum (Ⅲ)of tacrine[J]. Neurochem Int, 1998, 32: 273-279. doi: 10.1016/S0197-0186(97)00095-8http://doi.org/10.1016/S0197-0186(97)00095-8.

杨红光, 郑玉新, 梁友信.铝对神经行为功能和单胺类神经递质含量的影响[J].中华预防医学杂志, 1998, 32(2): 82-84.

何淑嫦, 邵枫, 牛侨, 等.铝染毒大鼠的学习记忆和氨基酸类神经递质的改变[J].中国行为医学科学, 2005, 14(1): 21-22, 43.

贾怡昌, 钟才云, 王颖明, 等.铝对大鼠海马氨基酸类神经递质含量的影响[J].中华预防医学杂志, 2001, 35(6): 397-400.

BHARATHI , SHAMASUNDAR NM, SATHYANARAYANA RAO TS, et al. A new insight on Al-maltolate-treated aged rabbit as Alzheimer's animal model[J]. Brain Res Brain Res Rev, 2006, 52(2): 275-292.

牛丕业, 何淑嫦, 牛侨.天麻对染铝大鼠大脑皮质SOD和MDA的影响[J], 环境与职业医学, 2003, 20(5): 357-359.

张勤丽, 牛丕业, 牛侨, 等.铝对体外培养神经元线粒体的影响[J].卫生研究, 2005, 34(6): 675-677.

DELEERS M. Cationic atmosphere and cation competition binding at negatively charged membranes: pathological implications of aluminum[J]. Res Commun Chem Pathol Pharmacol, 1985, 49(2): 277-294.

MATYJA E. Aluminum enhances glutamate-mediated neurotoxicity in organotypic cultures of rat hippocampus. Folia Neuropathol[J]. Folia Neuropathologica, 2000, 38(2): 47-53.

SAVORY J, HERMAN MM, GHRIBI O. Intracellular mechanisms underlying aluminum-induced apoptosis in rabbit brain[J]. J Inorg Biochem, 2003, 97(1): 151-154.

杨艳旭, 牛侨.慢性铝接触大鼠不同bcl-2脑区基因的表达[J].环境与职业医学, 2002, 19(4): 209-212, 218.

王林平, 牛侨, 陈艺兰, 等.铝致大鼠海马神经细胞凋亡及对Bcl-2和Bax表达的影响[J].环境与职业医学, 2005, 22(3): 225-228.

牛侨, 王林平, 陈艺兰, 等.铝作用下海马神经细胞凋亡及对Bcl-2和Bax基因转录的关系[J].卫生研究, 2005, 34(6): 671-674.

SAVORY J, RAO JKS, HUANG Y, et al. Age-related hippocampl changes in Bcl-2: Bax ratio, oxidative stress, redox-active iron and apoptosis associated with aluminum-induced neurodegeneration: increased susceptibility with aging[J]. Neurotoxicology, 1999, 20(5): 805-817.

GHRIBI O, HERMAN MM, SPAULDING NK, et al. Lithium inhibits aluminum-induced apotosis in rabbit hippocampus, by preventingcytochrome c translocation, Bcl-2decrease, Baxelevationand caspase-3 activation[J]. J Neurochem, 2002, 82(1): 137-145.

ZILKOVA M, KOSON P, ZILKA N. The hunt for dying neurons: insight into the neuronal loss in Alzheimer's disease[J]. Bratisl Lek Listy, 2006, 107(9-10): 366-373.

DEGTEREV A, HUANG Z, BOYCE M. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury[J]. Nat Chem Biol, 2005, 1(2): 112-119.

TENG X, DEGTEREV A, JAGTAP P, et al. Structure-activity relationship study of novel necroptosis inhibitors[J]. Bioorg Med Chem Lett, 2005, 15(22): 5039-5044.

牛侨, 张勤丽, 刘承芸, 王亮.程序性坏死在铝致SHSY5Y细胞死亡中的作用[J].中华预防医学杂志, 2009, (2): 132-136.

张勤丽, 牛侨, 郑金平, 等.程序性坏死参与铝致神经母细胞瘤细胞死亡机制[J].中国药理学与毒理学杂志, 2008, 22(5): 321-328.

Zhang QL, Niu Q, et al. Is necroptosis a death pathway in aluminum-induced neuroblastoma cell demise? [J]. Int J Immunopathol Pharmacol, 2008, 21(4): 787-796.

CHEN J, FAN R, WANG Y, et al. Progressive impairment of learning and memory in adult zebrafish treated by Al2O3nanoparticles when in embryos[J]. Chemosphere, 2020, 9(254): 126608. doi: 10.1016/j.chemosphere.2020.126608http://doi.org/10.1016/j.chemosphere.2020.126608.

CHENG L, YANG S, BAI J, NIU Q, et al. Aluminum maltolate triggers ferroptosis in neurons: mechanism of action[J]. Toxicol Mech Methods, 2021, 31(1): 33-42.

ABREO K, ABREO F, SELLA ML, et al. Aluminum enhances iron uptake and expression of neurofibrillary tangle protein in neuroblastoma cells[J]. J Neurochem, 1999, 72(5): 2059-2064.

SINGER, S M, CHAMBERS C B, et al. "Tau in A-luminum-induced Neurofibrillary Tangles."[J]. Neurotoxicology(Park Forest South), 1997, 18(1): 63-76.

EXLEY C. Aluminium and Alzheimer's Disease[M]. Oxford: Elsevier Science&Technology, 2001.

MULLER JP, BRUININK A. Neurotoxic effects of aluminium on embryonic chick brain cultures[J]. Acta Neuropathol(Berl), 1994, 88(4): 359-366.

HUANG T, GUO W, WANG Y, et al. Involvement of Mitophagy in Aluminum Oxide Nanoparticle-Induced Impairment of Learning and Memory in Mice[J]. Neurotox Res, 2021 Apr; 39(2): 378-391.

KWAHARA M, KATO M, KURODA Y. Effects of aluminium on the neurotoxicity of primary cultured neurons and on the aggregation of beta-amyloid protein[J]. Brain Res Bull, 2001, 55(20): 211-217.

王怀明, 杨望清, 郭洪志.铝盐致大鼠学习记忆功能障碍的β-APP、SS作用机制研究[J].临床神经病学杂志, 2001, 14(1): 24-26.

郭贵文, 吴亚兰, 杨小红, 等.氯化铝对大鼠脑组织胶质原酸性纤维蛋白和淀粉样β-蛋白前体基因的影响[J].中国药理学与毒理学杂志, 1999, 13(2): 227-230.

牛丕业.铝影响大鼠学习记忆的机制及天麻改善作用的研究[D].太原: 山西医科大学, 2003.

金涛, 夏满林, 邱锐, 等. Alzheimer's病铝中毒大鼠模型海马结构中β-APP和GFAP研究[J]. 苏州医学院学报, 2001, 21(2): 131-133.

冯改丰, 王唯析, 胡海涛, 等.铝中毒对SD大鼠海马结构内SS神经元的影响[J].微量元素与健康研究, 2002, 19(2): 6-7.

吴新荣, 朱小南, 陈汝筑. AlCl3对小鼠学习记忆和大鼠海马脑片长时程增强的影响[J]. 中国药理学和毒理学杂志, 2000, 14(6): 458-460.

RODELLA L, REZZANI R, LANZI R, et al. Chronic exposure to aluminium decreases NADPH-diaphorase positive neurons in the rat cerebral cortex[J]. Brain Res, 2001, 89(1-2): 229-233.

CHEN J, WANG M, RUAN D, et al. Early chronic aluminium exposure impairs long-term potentiation and depression to the rat dentate gyrus in vivo[J]. Neuroscience, 2002, 112(4): 879-887.

SHAFER TJ, NOSTRANDT AC, TILSON HA, et al. Mechanisms underlying AlCl3 inhibition of agonist-stimulated inositol phosphate accumulation: Role of calcium, G-proteins, phospholipase C and protein kinase C[J]. Biochem Pharmacol, 1994, 47(8): 1417-25.

PROVAN SD, YOKEL RA. Aluminum inhibits glutamatereleasefromtransverserathippocampal slices: role of G proteins, Ca channels and protein ki-nase C[J]. Neurotoxicology, 1992, 13(2): 413-420.

SHAFER T J, NOSTRANDT A C, TILSON H A, et al. RAluminum-induced DNA synthesis in osteoblasts: mediation by a G-protein coupled cation sensing mechanism[J]. J Cell Biochem, 1994, 56(1): 106-117.

CANALES JJ, CORBALAN R, MONTOLIU C, et al. Aluminium impairs the glutamate-nitric oxidecGMP pathway in cultured neurons and in rat brain in vivo: molecular mechanisms and implications for neuropathology[J]. J Inorg Biochem, 2001, 87(1-2): 63-69.

HERMENEGILDO C, SAEZ R, MINOIA C, et al. Chronic exposure to aluminium impairs the glutamate-nitric oxide-cyclic GMP pathway in the rat in vivo[J]. Neurochem Int, 1999; 34(3): 245-253.

王林平, 牛侨, 陈艺兰, 等.铝对大鼠海马神经细胞线粒体酶的影响[J].毒理学杂志, 2005, 19(4): 254-256.

NIU P Y, NIU Q, ZHANG QL. Aluminum impairs rat neural cell mitochondia in vitro[J]. Int J Immunopathol Pharmacol, 2005, 18(4): 683-689.

牛侨, 王林平, 陈艺兰, 等.铝作用下海马神经细胞凋亡及对Bcl-2和Bax基因转录的关系[J].卫生研究, 2005, 34(6): 671-674.

何淑嫦, 牛侨, 卲枫, 等.铝对原代培养神经细胞线粒体氧化功能的损伤[J].卫生研究, 2005, 34(6): 685-687.

贾志建, 路小婷, 潘宝龙, 等.慢性铝暴露对小鼠学习记忆及tau蛋白磷酸化的影响[J].环境与职业医学, 2012, 29(04): 203-209.

NIE J, FU X, NIU Q, et al. Effects of Al Exposure on Mitochondrial Dynamics in Rat Hippocampus[J]. Neurotox Res, 2019 Aug, 36(2): 334-346.

宋斐翡.职业铝接触对携带ApoEε4基因的作业工人认知功能的影响及tau蛋白表达的变化[D].太原: 山西医科大学, 2014.

ZHANG T, WANG S, NIU Q. Effect of Aluminum-Maltolate on the Content of AβProtein and the Expression of ApoER2, VLDLRs, and LRP1 in PC12-ApoE4 Cells[J]. Neurotox Res, 2019, 35(4): 931-944.

秦秀军. ApoE4基因与铝联合作用对小鼠认知功能损伤及机制研究[D]. 太原: 山西医科大学, 2020.

YANG X, YUAN Y, LU X, et al. The Relationship BetweenCognitiveImpairmentandGlobalDNA Methylation Decrease Among Aluminum Potroom Workers[J]. J Occup Environ Med, 2015 Jul, 57(7): 7-713.

PAN B, ZHOU Y, LI H, et al. Relationship between occupational aluminium exposure and histone lysine modification through methylation[J]. Trace Elem Med Biol, 2020 May, 18(61): 126-551.

LI H, XUE X, LI Z, et al. Aluminium-induced synaptic plasticity injury via the PHF8-H3K9me2-BDNF signalling pathway[J]. Chemosphere, 2020 Apr, 244, 125-445.

WANG F, KANG P, LI Z, et al. Role of MLL in the modification of H3K4me3 in aluminium-induced cognitive dysfunction[J]. Chemosphere, 2019 Oct, 232: 121-129.

XU Y, ZHANG H, PAN B, et al. Transcriptome-Wide Identification of Differentially Expressed Genes and Long Non-coding RNAs in Aluminum-Treated Rat Hippocampus[J]. Neurotox Res, 2018 Aug, 34(2): 220-232.

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