儿童铝负荷状况及铝神经毒作用机制的研究进展

裴静; 张立丰

doi:10.16835/j.cnki.1000-9817.2022.11.037

儿童铝负荷状况及铝神经毒作用机制的研究进展

doi: 10.16835/j.cnki.1000-9817.2022.11.037

裴静,
张立丰^,

沈阳医学院公共卫生学院儿少卫生与妇幼保健学教研室，辽宁 110034

基金项目:

国家自然科学基金面上项目 81673226

辽宁省科技厅科学技术研究项目 201601226

辽宁省教育厅科学技术研究面上项目 LJKZ1146

详细信息

作者简介:
裴静(1998-)，女，四川巴中人，在读硕士，主要研究方向为金属毒物对儿童少年认知能力的影响

通讯作者:
张立丰，E-mail：zgykdxzlf@163.com

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R446 R179
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- 文章访问数: 399
- HTML全文浏览量: 137
- PDF下载量: 36
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-30
- 修回日期: 2022-04-28
- 网络出版日期: 2022-11-30
- 刊出日期: 2022-11-25

Research progress on aluminum load in children and the mechanism of aluminum neurotoxicity

PEI Jing,
ZHANG Lifeng^,

Department of Maternal, Child and Adolescent Health, School of Public Health, Shenyang Medical College, Shenyang (110034), China

摘要

摘要: 铝是一种慢性蓄积性环境神经毒物。随着人体铝接触途径的多样化和不可避免性，其铝负荷水平呈上升趋势，长期铝负荷导致的神经生物毒性受到广泛关注。对于生长发育迅速的儿童来说，铝摄入量、铝吸收率以及体内铝负荷水平往往高于普通成人。长期持续低剂量铝负荷可能给儿童神经发育功能造成各种慢性亚临床损害及远期不可逆危害。鉴于以上背景，本文主要从儿童铝负荷状况、铝负荷对其神经发育功能的影响及神经发育功能受损相关机制的研究进展等方面进行阐述，为预防或治疗儿童铝负荷引起的健康问题提供理论依据，同时为儿童预防保健工作提供发展思路。
- 铝 /
- 全身负荷 /
- 中毒 /
- 儿童
Abstract: Aluminum is a chronic and cumulative environmental neurotoxin. Human exposure to aluminum is inevitable and impossible to quantify. The level of aluminum load is on the rise, the neurobiological toxicity of which is a cause for great concern. Aluminum intake, absorption, and load levels in the body are often higher in children in stages of rapid growth and development than in ordinary adults. Long-term low-dose aluminum load levels may cause a variety of chronic subclinical damage and long-term irreversible damage to the neurodevelopmental function of children. Therefore, this review primarily elucidates the status of aluminum load in children and its effect on neurodevelopmental functioning. Furthermore, we examine research progress on the related mechanism of impaired neurodevelopmental functioning so as to provide a theoretical basis for the treatment and prevention of health problems caused by aluminum load in children and outline proposals for healthcare in this area.
- Aluminum /
- Body burden /
- Poisoning /
- Child
注释:

1) 利益冲突声明 所有作者声明无利益冲突。

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参考文献(52)

[1]	张玉华, 刘于飞, 张维蔚, 等. 2014-2018年广州市市售食品中铝含量调查及人群膳食暴露评估[J]. 现代预防医学, 2020, 47(11): 1967-1969, 1974. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202011014.htm ZHANG Y H, LIU Y F, ZHANG W W, et al. Investigation on aluminum content and dietary exposure assessment of food sold in Guangzhou from 2014 to 2018[J]. Mod Prev Med, 2020, 47(11): 1967-1969, 1974. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202011014.htm
[2]	THOMAS T, ARIANE L, ANNA E K, et al. Aggregated aluminum exposure: risk assessment for the general population[J]. Arch Toxicol, 2019, 93(12): 3503-3521. doi: 10.1007/s00204-019-02599-z
[3]	PETO M V. Aluminum and Iron in humans: bioaccumulation, pathology, and removal[J]. Rejuven Res, 2010, 13(5): 589-598. doi: 10.1089/rej.2009.0995
[4]	WANG X M, CHENG D, JIANG W B, et al. Mechanisms underlying aluminum neurotoxicity related to 14-3-3 protein[J]. Toxicol Sci, 2018, 163(1): 45-56. doi: 10.1093/toxsci/kfy021
[5]	ZHANG J, HUANG W Y, XU F B, et al. Iron dyshomeostasis participated in rat hippocampus toxicity caused by aluminum chloride[J]. Biol Trace Elem Res, 2020, 197(2): 580-590. doi: 10.1007/s12011-019-02008-7
[6]	斯冬芳, 刘梦丽, 卢国伟, 等. 绍兴市柯桥区2015—2019年部分市售食品中铝残留量的调查分析[J]. 中国卫生检验杂志, 2021, 31(8): 1008-1010. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ202108030.htm SI D F, LIU M L, LU G W, et al. Investigation and analysis of aluminum residues in some market foods in Keqiao District of Shaoxing City from 2015 to 2019[J]. Chin J Health Inspect, 2021, 31(8): 1008-1010. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ202108030.htm
[7]	GOASDOUÉ K, STEPHANIE M M, PAUL B C, et al. Review: the blood-brain barrier: protecting the developing fetal brain[J]. Placenta, 2017, 54: 111-116. doi: 10.1016/j.placenta.2016.12.005
[8]	张立实, 李晓蒙, 吴永宁. 我国食品安全风险评估及相关研究进展[J]. 现代预防医学, 2020, 47(20): 3649-3652. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202020001.htm ZHANG L S, LI X M, WU Y N. Food safety risk assessment and related research progress in China[J]. Mod Prev Med, 2020, 47(20): 3649-3652. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202020001.htm
[9]	CAO P, LIU A D, YANG D J, et al. Assessment of dietary exposure of young Chinese children to aluminum residues[J]. Food Addit Contam Part A Chem Anal Control Exp Risk Assess, 2019, 36(4): 582-591. doi: 10.1080/19440049.2019.1579369
[10]	吴春峰, 罗宝章, 朱珍妮, 等. 上海市中小学生膳食铝摄入量评估[J]. 环境与职业医学, 2018, 35(6): 500-505. doi: 10.13213/j.cnki.jeom.2018.17740 WU C F, LUO B Z, ZHU Z N, et al. Evaluation of dietary aluminum intake of primary and middle school students in Shanghai[J]. J Environ Occup, 2018, 35(6): 500-505. (in Chinese) doi: 10.13213/j.cnki.jeom.2018.17740
[11]	CORKINS M R. Aluminum effects in infants and children[J]. Pediatrics, 2019, 144(6): e20193148. doi: 10.1542/peds.2019-3148
[12]	HIROSHI Y, TOYOHARU T, KATSUHIKO S. Metallomics analysis for assessment of toxic metal burdens in infants/children and their mothers: early assessment and intervention are essential[J]. Biomolecules, 2020, 11(1): 6. doi: 10.3390/biom11010006
[13]	Joint FAO/WHO Expert Committee on Food Additives(JECFA). Summary report of the seventy-fourth meeting of JECFA[R]. Geneva: WHO, 2011.
[14]	DANIELA F, ROSSANO A, CLARA G, et al. Aluminum exposure and toxicity in neonates: a practical guide to halt aluminum overload in the prenatal and perinatal periods[J]. World J Pediatr, 2014, 10(2): 101-107. doi: 10.1007/s12519-014-0477-x
[15]	SIROT V, THIEMA T, THIERRY G, et al. French infant total diet study: exposure to selected trace elements and associated health risks[J]. Food Chem Toxicol, 2018, 120: 625-633. doi: 10.1016/j.fct.2018.07.062
[16]	王艳敏, 周鸿, 熊丽, 等. 江西省婴幼儿谷类辅食中14种元素污染状况调查[J]. 现代预防医学, 2021, 48(11): 1955-1958, 2093. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202111010.htm WANG Y M, ZHOU H, XIONG L, et al. Investigation on the pollution status of 14 elements in cereal supplementary food of infants and young children in Jiangxi Province[J]. Mod Prev Med, 2021, 48(11): 1955-1958, 2093. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202111010.htm
[17]	杨乐, 邢宏宇, 单美娜, 等. 内蒙古自治区居民膳食中铝暴露风险评估[J]. 中国食品卫生杂志, 2021, 33(2): 196-200. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSPZ202102017.htm YANG L, XING H Y, SHAN M N, et al. Risk assessment of dietary aluminum exposure among residents in Inner Mongolia Autonomous Region[J]. Chin J Food Hygien, 2021, 33(2): 196-200. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZSPZ202102017.htm
[18]	聂晓玲, 王敏娟, 刘宇, 等. 2013-2015年陕西省居民膳食铝暴露评估[J]. 卫生研究, 2018, 47(2): 307-311. https://www.cnki.com.cn/Article/CJFDTOTAL-WSYJ201802027.htm NIE X L, WANG M J, LIU Y, et al. Dietary aluminum exposure assessment of residents in Shaanxi Province from 2013 to 2015[J]. Health Res, 2018, 47(2): 307-311. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-WSYJ201802027.htm
[19]	牛婷, 刘健, 康玲, 等. 2016-2017年乌鲁木齐市大气细颗粒物中铝污染现状及其健康风险评价[J]. 职业与健康, 2019, 35(4): 521-524, 527. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJK201904022.htm NIU T, LIU J, KANG L, et al. Aluminum pollution status and health risk assessment of atmospheric fine particles in Urumqi from 2016 to 2017[J]. Occup Health, 2019, 35(4): 521-524, 527. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJK201904022.htm
[20]	MEYER C M C, RODRÍGUEZ J M, CARPIO E A, et al. Arsenic, manganese and aluminum contamination in groundwater resources of Western Amazonia(Peru)[J]. Sci Total Environ, 2017(607/608): 1437-1450.
[21]	NICOLA P, SUSANNA E. Aluminum in vaccines: does it create a safety problem?[J]. Vaccine, 2018, 36(39): 5825-5831. doi: 10.1016/j.vaccine.2018.08.036
[22]	SHAW C A, LI Y, TOMLJENOVIC L. Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes[J]. J Inorg Biochem, 2013, 128: 237-244. doi: 10.1016/j.jinorgbio.2013.07.022
[23]	MELENDEZ L, SANTOS D, POLIDO L, et al. Aluminium and other metals may pose a risk to children with autism spectrum disorder: biochemical and behavioural impairments[J]. Clin Exp Pharmacol, 2013, 3(1): 1-9.
[24]	TOMLJENOVIC L, SHAW C A. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations[J]. Lupus, 2012, 21(2): 223-230. doi: 10.1177/0961203311430221
[25]	MOVSAS T Z, PANETH N, WILSON R, et al. Effect of routine vaccination on aluminum and essential element levels in preterm infants[J]. JAMA Pediatr, 2013, 167(9): 870-872. doi: 10.1001/jamapediatrics.2013.108
[26]	LETZEL M, DREXLER H, THOMAS G, et al. Impact of daily antiperspirant use on the systemic aluminum exposure: an experimental intervention study[J]. Skin Pharmacol Physiol, 2020, 33(1): 1-8. doi: 10.1159/000502239
[27]	MARTINEZ C S, GEMA V, JOSÉ A U O, et al. Aluminum exposure for 60 days at an equivalent human dietary level promotes peripheral dysfunction in rats[J]. J Inorg Biochem, 2018, 181: 169-176. doi: 10.1016/j.jinorgbio.2017.08.011
[28]	张立丰, 白春玉, 张迪, 等. 亚慢性铝暴露对Wistar大鼠学习记忆及海马CA1区c-fos表达的影响[J]. 中国药理学与毒理学杂志, 2016, 30(5): 553-557. https://www.cnki.com.cn/Article/CJFDTOTAL-YLBS201605013.htm ZHANG L F, BAI C Y, ZHANG D, et al. Effects of subchronic aluminum exposure on learning and memory and c-fos expression in hippocampal CA1 region of Wistar rats[J]. Chin J Pharmacol Toxicol, 2016, 30(5): 553-557. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-YLBS201605013.htm
[29]	杨小雪, 谢春, 张华, 等. 妊娠期至成年期氟铝联合暴露对仔鼠生理和神经发育及学习记忆能力的影响[J]. 环境与健康杂志, 2014, 31(9): 773-776. https://www.cnki.com.cn/Article/CJFDTOTAL-HJYJ201409008.htm YANG X X, XIE C, ZHANG H, et al. Effects of combined exposure of fluoride and aluminum from pregnancy to adulthood on physiological and neurological development and learning and memory ability of offspring[J]. J Environ Health, 2014, 31(9): 773-776. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-HJYJ201409008.htm
[30]	葛启迪, 张华, 谢春, 等. 孕哺期至成年前铝暴露对子鼠空间学习记忆能力和海马miR-132转录的影响[J]. 环境与职业医学, 2018, 35(8): 761-766. https://www.cnki.com.cn/Article/CJFDTOTAL-LDYX201808018.htm GE Q D, ZHANG H, XIE C, et al. Effects of aluminum exposure from gestation and lactation to adulthood on spatial learning and memory ability and hippocampal miR-132 transcription in offspring[J]. J Environ Occup, 2018, 35(8): 761-766. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-LDYX201808018.htm
[31]	蒋鸫, 康朝胜, 余资江. 孕期染铝对仔鼠脑皮质神经元的影响[J]. 局解手术学杂志, 2011, 20(2): 142-144. https://www.cnki.com.cn/Article/CJFDTOTAL-JJXZ201102015.htm JIANG D, KANG C S, YU Z J. Effects of exposure to aluminum during pregnancy on cerebral cortical neurons of newborn rats[J]. J Local Surg, 2011, 20(2): 142-144. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-JJXZ201102015.htm
[32]	ZHANG L F, JIN C H, LIU Q F, et al. Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats[J]. J Toxicol Sci, 2013, 38(2): 255-268.
[33]	GASEM M A T, JAMAAN S A, MOHAMMAD A. Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring[J]. Pharmacol Biochem Behav, 2012, 101(1): 49-56.
[34]	SULAIMAN R, WANG M, REN X F. Exposure to aluminum, cadmium, and mercury and autism spectrum disorder in children: a systematic review and Meta-analysis[J]. Chem Res Toxicol, 2020, 33(11): 2699-2718.
[35]	MCLACHLAN D R C, BERGERON C, ALEXANDROV P N, et al. Aluminum in neurological and neurodegenerative disease[J]. Mol Neurobiol, 2019, 56(2): 1531-1538.
[36]	KANEKO N, SUGIOKA T, SAKURAI H. Aluminum compounds enhance lipid peroxidation in liposomes: insight into cellular damage caused by oxidative stress[J]. J Inorg Biochem, 2007, 101(6): 967-975.
[37]	CELIK H, CELIK N, KOCYIGIT A, et al. The relationship between plasma aluminum content, lymphocyte DNA damage, and oxidative status in person using aluminum containers and utensils daily[J]. Clin Biochem, 2012, 45(18): 1629-1633.
[38]	蔺庆伟, 马剑敏, 彭雪, 等. 环境中铝来源、铝毒机制及影响因子研究进展[J]. 生态环境学报, 2019, 28(9): 1915-1926. https://www.cnki.com.cn/Article/CJFDTOTAL-TRYJ201909025.htm LIN Q W, MA J M, PENG X, et al. Research progress on the source, toxicity mechanism and influencing factors of aluminum in the environment[J]. J Ecolog Environ, 2019, 28(9): 1915-1926. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-TRYJ201909025.htm
[39]	ZHUANG C C, SHE Y, ZHANG H Y, et al. Cytoprotective effect of deferiprone against aluminum chloride-induced oxidative stress and apoptosis in lymphocytes[J]. Toxicol Lett, 2018, 285: 132-138.
[40]	GUPTA V B, ANITHA S, HEGDE M L, et al. Aluminum in Alzheimer's disease: are we still at a crossroad?[J]. Cell Mol Life Sci, 2005, 62(2): 143-158.
[41]	薛星莉, 李欢, 李亚芹, 等. 亚慢性铝暴露抑制大鼠海马区突触可塑性PI3K/AKT/mTOR信号通路机制[J]. 中国职业医学, 2020, 47(2): 141-146. https://www.cnki.com.cn/Article/CJFDTOTAL-XYYX202002007.htm XUE X L, LI H, LI Y Q, et al. Subchronic aluminum exposure inhibits PI3K/AKT/mTOR signal pathway of synaptic plasticity in hippocampus of rats[J]. Chin Occupat Med, 2020, 47(2): 141-146. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-XYYX202002007.htm
[42]	张淑惠, 张慧芳, 徐义荣, 等. 慢性铝染毒对大鼠海马突触可塑性及神经连接蛋白1表达的影响[J]. 环境与职业医学, 2019, 36(7): 621-626. https://www.cnki.com.cn/Article/CJFDTOTAL-LDYX201907004.htm ZHANG S H, ZHANG H F, XU Y R, et al. Effects of chronic aluminum exposure on synaptic plasticity and expression of connexin 1 in hippocampus of rats[J]. J Environ Occup, 2019, 36(7): 621-626. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-LDYX201907004.htm
[43]	高婷, 夏欣宇, 袁春满, 等. 亚慢性染铝对大鼠海马PSD95及长时程增强的影响[J]. 环境与职业医学, 2019, 36(11): 995-1000. https://www.cnki.com.cn/Article/CJFDTOTAL-LDYX201911002.htm GAO T, XIA X Y, YUAN C M, et al. Effects of subchronic exposure to aluminum on hippocampal PSD95 and long-term potentiation in rats[J]. J Environ Occup, 2019, 36(11): 995-1000. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-LDYX201911002.htm
[44]	WANG Y N, LI H, ZHANG J S, et al. Effect of aluminum combined with ApoEε4 on Tau phosphorylation and Aβ deposition[J]. J Trace Elem Med Biol, 2021, 64: 126700.
[45]	LUCAS J J, HERNÁNDEZ F, GÓMEZ-RAMOS P, et al. Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3 beta conditional transgenic mice[J]. EMBO J, 2001, 20(1/2): 27-39.
[46]	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, 34(2): 220-232.
[47]	WANG F, KANG P, LI Z Y, et al. Role of MLL in the modification of H3K4me3 in aluminum-induced cognitive dysfunction[J]. Chemosphere, 2019, 232: 121-129.
[48]	LI H, XUE X L, LI Z Y, et al. Aluminium-induced synaptic plasticity injury via the PHF8-K3K9me2-BDNF signalling pathway[J]. Chemosphere, 2020, 244: 125455.
[49]	MUHAMMAD F I, SYEDA M F, AAMRA M, et al. Expression of DnMTs and MBDs in AlCl3-Induced neurotoxicity mouse model[J]. Biol Trace Elem Res, 2021, 199(9): 3433-3444.
[50]	国家卫生和计划生育委员会. 食品安全国家标准食品添加剂使用标准: GB2760—2014[S]. 北京: 国家标准出版社, 2014. National Health and Family Planning Commission of the PRC. National standards for food safety-standards for the use of food additives: GB 2760-2014[S]. Beijing: National Standards Press, 2014. (in Chinese)
[51]	李杉, 付鹏钰, 杨丽, 等. 2013-2017年河南省食品中铝含量及本底值调查[J]. 中国预防医学杂志, 2020, 21(4): 439-441. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYC202004021.htm LI S, FU P Y, YANG L, et al. Investigation on aluminum content and background value of food in Henan Province from 2013 to 2017[J]. Chin Prev Med, 2020, 21(4): 439-441. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYC202004021.htm
[52]	WANG B, LIU Y, WANG H, et al. Contamination and health risk assessment of lead, arsenic, cadmium, and aluminum from a total diet study of Jilin Province, China[J]. Food Sci Nutr, 2020, 8(10): 5631-5640.