谷氨酸代谢转运障碍和氧化损伤在甲基汞神经毒性中的交互作用及其分子机制
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摘要
通过动物整体实验和体外神经胶质细胞和神经原培养,观察甲基汞的神经毒性以及11种不同物质预处理对甲基汞神经毒性作用的影响。研究结果揭示了谷氨酸代谢转运障碍和氧化损伤在甲基汞神经毒性中的交互作用,为阐明甲基汞神经毒性作用的分子机制,防治甲基汞中毒提供实验依据。
The neurotoxicity of methylmercury(MeHg) and the effects of 11 different materials pretreatment on MeHg neurotoxicity were investigated with the animal experiment and cerebral cortex astrocyte and neuron culture. The study results revealed the interactions between metabolic and transport impediment of glutamate and oxidative damage,elucidated the molecular mechanism of MeHg neurotoxicity and provided experimental basis for the prevention and treatment of the MeHg poisoning.
The neurotoxicity of methylmercury(MeHg) and the effects of 11 different materials pretreatment on MeHg neurotoxicity were investigated with the animal experiment and cerebral cortex astrocyte and neuron culture. The study results revealed the interactions between metabolic and transport impediment of glutamate and oxidative damage,elucidated the molecular mechanism of MeHg neurotoxicity and provided experimental basis for the prevention and treatment of the MeHg poisoning.
引文
[1]Hansen JC,Danscher G.Organic mercury:an environmental threat to the health of dietary-exposed societies?[J].Rev Environ Health,1997,12(2):107-116.
[2]Atchison WD.Is chemical neurotransmission altered specifically during methylmercury-induced cerebellar dysfunction?[J].Trends Pharmacol Sci,2005,26(11):549-557.
[3]Sattler R,Tymianski M.Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death[J].Mol Neurobiol,2001,24(1-3):107-129.
[4]Seal RP,Amara SG.Excitatory amino acid transports:a family in flux[J].Annu Rev Pharmacol Toxicol,1999,39:431-456.
[5]O′Shea RD.Roles and regulation of glutamate transporters in the central nervous system[J].Clin Exp Phamacol Physiol,2002,29(11):1018-1023.
[6]Otis TS,Brasnjo G,Dzubay JA,et al.Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex[J].Neurochem Int,2004,45(4):537-544.
[7]Stephenson FA,Cousins SL,Kenny AV.Assembly and forward trafficking of NMDA receptors[J].Mol Membr Biol,2008,25(4):311-320.
[8]Fitsanakis VA,Aschner M.The importance of glutamate,glycine,andγ-aminobutyric acid transport and regulation in manganese,mercury and lead neurotoxicity[J].Toxicol Appl Pharmacol,2005,204(3):343-354.
[9]田雅文,徐兆发.谷氨酸与甲基汞的神经毒性[J].毒理学杂志,2010,24(4):328-331.
[10]Roos DH,Puntel RL,Santos MM,et al.Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices:involvement of oxidative stress and glutamatergic system[J].Toxicol In Vitro,2009,23(2):302-307.
[11]Yin Z,Albrecht J,Syversen T,et al.Comparison of alterations in amino acids content in cultured astrocytes or neurons exposed to methylmercury separately or in co-culture[J].Neurochem Int,2009,55(1-3):136-142.
[12]Farina M,Dahm KC,Schwalm FD,et al.Methylmercury increases glutamate release from brain synaptosomes and glutamate uptake by cortical slices from suckling rat pups:modulatory effect of ebselen[J].Toxicol Sci,2003,73(1):135-140.
[13]黄焱明,徐兆发.甲基汞对谷氨酸代谢转运影响的研究进展[J].环境与健康杂志,2010,27(9):836-838.
[14]Jaiswal AK.Nrf2 signaling in coordinated activation of antioxidant gene expression[J].Free Radic Biol Med,2004,36(10):1199-1207.
[15]Copple IM,Goldring CE,Kitteringham NR,et al.The Nrf2-Keap1 defence pathway:role in protection against drug-induced toxicity[J].Toxicology,2008,246(1):24-33.
[16]Kobayashi A,Ohta T,Yamamoto M.Unique function of the Nrf2-keap1 pathway in the inducible expression of antioxidant and detoxifying enzynmes[J].Methods Enzymol,2004,378:273-286.
[17]Kensler TW,Wakabayashi N,Biswal S.Cell survival responses to environmental stresses via the Keal1-Nrf2-ARE pathway[J].Annu Rev Pharmacol Toxicol,2007,47:89-116.
[18]Yin Z,Milatovic D,Aschner JL,et al.Methylmercury induces oxidative injury,alterations in permeability and glutamine transport in cultured astrocytes[J].Brain Res,2007,1131(1):1-10.
[19]Ni M,Li X,Yin Z,et al.Methylmercury induces acute oxidative stress,altering Nrf2 protein level in primary microglial cells[J].Toxicol Sci,2010,116(2):590-603.
[20]Wang L,Jiang H,Yin Z,et al.Methylmercury toxicity and Nrf2-dependent detoxification in astrocytes[J].Toxicol Sci,2009,107(1):135-143.
[21]Toyama T,Sumi D,Shinkai Y,et al.Cytoprotective role of Nrf2/Keap1 system in methylmercury toxicity[J].Biochem Biophys Res Commun,2007,363(3):645-650.
[22]Thomas DM,Kuhn DM.MK-801 and dextromethorphan block microglial activation and protect against methamphetamineinduced neurotoxicity[J].Brain Res,2005,1050(1-2):190-198.
[23]Xu Z,Jia K,Xu B,et al.Effects of MK-801,taurine and dextromethorphan on neurotoxicity caused by manganese in rats[J].Toxicol Ind Health,2010,26(1):55-60.
[24]Saxton J,Hofbauer RK,Woodward M,et al.Memantine and functional communication in Alzheimer′s disease:results of a12-week,international,randomized clinical trial[J].JAlzheimers Dis,2012,28(1):109-118.
[25]Xia P,Chen HS,Zhang D,et al.Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses[J].J Neurosci,2010,30(33):11246-11250.
[26]Thomas DM,Kuhn DM.MK-801 and dextromethorphan block microglial activation and protect againstmethamphetamineinduced neurotoxicity[J].Brain Res,2005,1050(1-2):190-198.
[27]Shin EJ,Nah SY,Chae JS,et al.Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats[J].Neurochem Int,2007,50(6):791-799.
[28]Lacomblez L,Bensimon G,Leigh PN,et al.Dose-ranging study of riluzole in amyotrophic lateral sclerosis.Amyotrophic Lateral Sclerosis/Riluzole Study GroupⅡ[J].Lancet,1996,347(9013):1425-1431.
[29]Zarate CA,Manji HK.Riluzole in psychiatry:a systematic review of the literature[J].Expert Opin Drug Metab Toxicol,2008,4(9):1223-1234.
[30]Frizzo ME,Dall′Onder LP,Dalcin KB,et al.Riluzole enhances glutamate uptake in rat astrocyte cultures[J].Cell Mol Neurobiol,2004,24(1):123-128.
[31]Irifune M,Kikuchi N,Saida T,et al.Riluzole,a glutamate release inhibitor,induces loss of righting reflex,antinociception,and immobility in response to noxious stimulation in mice[J].Anesth Analg,2007,104(6):1415-1421.
[32]Fumagalli E,Funicello M,Rauen T,et al.Riluzole enhances the activity of glutamate transporters GLAST,GLT1 and EAAC1[J].Eur J Pharmacol,2008,578(2-3):171-176.
[33]Toklu HZ,Uysal MK,Kabasakal L,et al.The effects of riluzole on neurological,brain biochemical,and histological changes in early and late term of sepsis in rats[J].J Surg Res,2009,152(2):238-248.
[34]Chen WQ,Jin H,Nguyen M,et al.Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons[J].J Neurosci Res,2001,66(4):612-619.
[35]Zafarullah M,Li WQ,Sylvester J,et al.Molecular mechanisms of N-acetylcysteine actions[J].Cell Mol Life Sci,2003,60(1):6-20.
[36]Gegelashvili G,Schousboe A.High affinity glutamate transporters:regulation of expression and activity[J].Mol Pharmacol,1997,52(1):6-15.
[37]Danbolt NC.Glutamate uptake[J].Prog Neurobiol,2001,65(1):1-105.
[38]Xu B,Xu ZF,Deng Y,et al.Protective effects of MK-801 on methylmercury-induced neuronal injury in rat cerebral cortex:involvement of oxidative stress and glutamate metabolism dysfunction[J].Toxicology,2012,300(3):112-120.
[39]Xu B,Xu ZF,Deng Y,et al.MK-801 protects against intracellular Ca2+overloading and improves N-methyl-D-aspartate receptor expression in cerebral cortex of methylmercury-poisoned rats[J].J Mol Neurosci,2013,49(1):162-171.
[40]Liu W,Xu Z,Deng Y,et al.Protective effects of memantine against methylmercury-induced glutamate dyshomeostasis and oxidative stress in rat cerebral cortex[J].Neurotox Res,2013,24(3):320-337.
[41]Liu W,Xu Z,Yang T,et al.Memantine,a low-affinity NMDAreceptor antagonist,protects against methylmercury-induced cytotoxicity of rat primary cultured cortical neurons,involvement of Ca2+dyshomeostasis antagonism,and indirect antioxidation effects[J].Mol Neurobiol,2017,54(7):5034-5050.
[42]Feng S,Xu Z,Liu W,et al.Preventive effects of dextromethorphan on methylmercury-induced glutamate dyshomeostasis and oxidative damage in rat cerebral cortex[J].Biol Trace Elem Res,2014,159(1-3):332-345.
[43]Xu Z,Jia K,Xu B,et al.Effects of MK-801,taurine and dextromethorphan on neurotoxicity caused by manganese in rats[J].Toxicol Ind Health,2010,26(1):55-60.
[44]Deng Y,Xu Z,Liu W,et al.Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex[J].Oxid Med Cell Longev,2012,2012:534705.
[45]Deng Y,Xu Z,Xu B,et al.Exploring cross-talk between oxidative damage and excitotoxicity and the effects of riluzole in the rat cortex after exposure to methylmercury[J].Neurotox Res,2014,26(1):40-51.
[46]李乐慧,徐兆发,奉姝,等.牛磺酸对甲基汞染毒大鼠脑皮质Nrf2及HO-1、γ-GCS、GPx-1表达的影响[J].中国工业医学杂志,2013,26(3):163-166.
[47]李乐慧,徐兆发,刘巍,等.牛磺酸对甲基汞致大鼠脑谷氨酸代谢转运障碍的保护作用[J].实用预防医学,2014,21(3):261-263.
[48]李乐慧,徐兆发,刘巍,等.牛磺酸对甲基汞致大鼠脑氧化损伤的保护作用[J].环境与职业医学,2014,31(6):469-471,475.
[49]魏衍刚,徐兆发,邓宇,等.N-乙酰半胱氨酸对甲基汞致大鼠脑皮质氧化损伤和谷氨酸代谢障碍的影响[J].毒理学杂志,2012,26(2):79-83.
[50]魏衍刚,徐兆发,徐斌,等.N-乙酰半胱氨酸对甲基汞致大鼠脑皮质氧化损伤的影响[J].环境与健康杂志,2013,30(3):193-197,283.
[51]Yang TY,Xu ZF,Liu W,et al.Alpha-lipoic acid protects against methylmercury-induced neurotoxic effects via inhibition of oxidative stress in rat cerebral cortex[J].Environ Toxicol Pharmacol,2015,39(1):157-166.
[52]Yang T,Xu Z,Liu W,et al.Protective effects of alpha-lipoic acid on MeHg-induced oxidative damage and intracellular Ca2+dyshomeostasis in primary cultured neurons[J].Free Radic Res,2016,50(5):542-556.
[53]Yang T,Xu Z,Liu W,et al.Alpha-lipoic acid reduces ethylmercury-induced neuronal injury in rat cerebral cortex via antioxidation pathways[J].Environ Toxicol,2017,32(3):931-943.
[54]Liu W,Xu Z,Deng Y,et al.Excitotoxicity and oxidative damages induced by methylmercury in rat cerebral cortex and the protective effects of tea polyphenols[J].Environ Toxicol,2014,29(3):269-283.
[55]Liu W,Xu Z,Yang T,et al.The protective role of tea polyphenols against methylmercury-induced neurotoxic effects in rat cerebral cortex via inhibition of oxidative stress[J].Free Radic Res,2014,48(8):849-863.
[56]Liu W,Xu Z,Yang T,et al.Tea polyphenols protect against methylmercury-induced cell injury in rat primary cultured astrocytes,involvement of oxidative stress and glutamate uptake/metabolism disorders[J].Mol Neurobiol,2016,53(5):2995-3009.
[57]Yang H,Xu Z,Liu W,et al.Effect of grape seed proanthocyanidin extracts on methylmercury-induced neurotoxicity in rats[J].Biol Trace Elem Res,2012,147(1-3):156-164.
[58]Feng S,Xu Z,Wang F,et al.Sulforaphane prevents methylmercury-induced oxidative damage and excitotoxicity through activation of the Nrf2-ARE pathway[J].Mol Neurobiol,2017,54(1):357-391.
[59]奉姝,徐兆发,王飞,等.莱菔硫烷与右美沙芬联合应用对甲基汞致大鼠神经毒性的影响[J].环境与健康杂志,2015,32(8):663-667.
[60]徐兆发,奉姝,王飞,等.SFN和CUR对甲基汞致大鼠脑谷氨酸代谢转运及氧化损伤的影响[A]//中国环境科学学会.2016年中国环境科学学会学术年会论文集[C].海口:中国环境科学学会,2016:4287-4291.2018-12-12
[2]Atchison WD.Is chemical neurotransmission altered specifically during methylmercury-induced cerebellar dysfunction?[J].Trends Pharmacol Sci,2005,26(11):549-557.
[3]Sattler R,Tymianski M.Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death[J].Mol Neurobiol,2001,24(1-3):107-129.
[4]Seal RP,Amara SG.Excitatory amino acid transports:a family in flux[J].Annu Rev Pharmacol Toxicol,1999,39:431-456.
[5]O′Shea RD.Roles and regulation of glutamate transporters in the central nervous system[J].Clin Exp Phamacol Physiol,2002,29(11):1018-1023.
[6]Otis TS,Brasnjo G,Dzubay JA,et al.Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex[J].Neurochem Int,2004,45(4):537-544.
[7]Stephenson FA,Cousins SL,Kenny AV.Assembly and forward trafficking of NMDA receptors[J].Mol Membr Biol,2008,25(4):311-320.
[8]Fitsanakis VA,Aschner M.The importance of glutamate,glycine,andγ-aminobutyric acid transport and regulation in manganese,mercury and lead neurotoxicity[J].Toxicol Appl Pharmacol,2005,204(3):343-354.
[9]田雅文,徐兆发.谷氨酸与甲基汞的神经毒性[J].毒理学杂志,2010,24(4):328-331.
[10]Roos DH,Puntel RL,Santos MM,et al.Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices:involvement of oxidative stress and glutamatergic system[J].Toxicol In Vitro,2009,23(2):302-307.
[11]Yin Z,Albrecht J,Syversen T,et al.Comparison of alterations in amino acids content in cultured astrocytes or neurons exposed to methylmercury separately or in co-culture[J].Neurochem Int,2009,55(1-3):136-142.
[12]Farina M,Dahm KC,Schwalm FD,et al.Methylmercury increases glutamate release from brain synaptosomes and glutamate uptake by cortical slices from suckling rat pups:modulatory effect of ebselen[J].Toxicol Sci,2003,73(1):135-140.
[13]黄焱明,徐兆发.甲基汞对谷氨酸代谢转运影响的研究进展[J].环境与健康杂志,2010,27(9):836-838.
[14]Jaiswal AK.Nrf2 signaling in coordinated activation of antioxidant gene expression[J].Free Radic Biol Med,2004,36(10):1199-1207.
[15]Copple IM,Goldring CE,Kitteringham NR,et al.The Nrf2-Keap1 defence pathway:role in protection against drug-induced toxicity[J].Toxicology,2008,246(1):24-33.
[16]Kobayashi A,Ohta T,Yamamoto M.Unique function of the Nrf2-keap1 pathway in the inducible expression of antioxidant and detoxifying enzynmes[J].Methods Enzymol,2004,378:273-286.
[17]Kensler TW,Wakabayashi N,Biswal S.Cell survival responses to environmental stresses via the Keal1-Nrf2-ARE pathway[J].Annu Rev Pharmacol Toxicol,2007,47:89-116.
[18]Yin Z,Milatovic D,Aschner JL,et al.Methylmercury induces oxidative injury,alterations in permeability and glutamine transport in cultured astrocytes[J].Brain Res,2007,1131(1):1-10.
[19]Ni M,Li X,Yin Z,et al.Methylmercury induces acute oxidative stress,altering Nrf2 protein level in primary microglial cells[J].Toxicol Sci,2010,116(2):590-603.
[20]Wang L,Jiang H,Yin Z,et al.Methylmercury toxicity and Nrf2-dependent detoxification in astrocytes[J].Toxicol Sci,2009,107(1):135-143.
[21]Toyama T,Sumi D,Shinkai Y,et al.Cytoprotective role of Nrf2/Keap1 system in methylmercury toxicity[J].Biochem Biophys Res Commun,2007,363(3):645-650.
[22]Thomas DM,Kuhn DM.MK-801 and dextromethorphan block microglial activation and protect against methamphetamineinduced neurotoxicity[J].Brain Res,2005,1050(1-2):190-198.
[23]Xu Z,Jia K,Xu B,et al.Effects of MK-801,taurine and dextromethorphan on neurotoxicity caused by manganese in rats[J].Toxicol Ind Health,2010,26(1):55-60.
[24]Saxton J,Hofbauer RK,Woodward M,et al.Memantine and functional communication in Alzheimer′s disease:results of a12-week,international,randomized clinical trial[J].JAlzheimers Dis,2012,28(1):109-118.
[25]Xia P,Chen HS,Zhang D,et al.Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses[J].J Neurosci,2010,30(33):11246-11250.
[26]Thomas DM,Kuhn DM.MK-801 and dextromethorphan block microglial activation and protect againstmethamphetamineinduced neurotoxicity[J].Brain Res,2005,1050(1-2):190-198.
[27]Shin EJ,Nah SY,Chae JS,et al.Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats[J].Neurochem Int,2007,50(6):791-799.
[28]Lacomblez L,Bensimon G,Leigh PN,et al.Dose-ranging study of riluzole in amyotrophic lateral sclerosis.Amyotrophic Lateral Sclerosis/Riluzole Study GroupⅡ[J].Lancet,1996,347(9013):1425-1431.
[29]Zarate CA,Manji HK.Riluzole in psychiatry:a systematic review of the literature[J].Expert Opin Drug Metab Toxicol,2008,4(9):1223-1234.
[30]Frizzo ME,Dall′Onder LP,Dalcin KB,et al.Riluzole enhances glutamate uptake in rat astrocyte cultures[J].Cell Mol Neurobiol,2004,24(1):123-128.
[31]Irifune M,Kikuchi N,Saida T,et al.Riluzole,a glutamate release inhibitor,induces loss of righting reflex,antinociception,and immobility in response to noxious stimulation in mice[J].Anesth Analg,2007,104(6):1415-1421.
[32]Fumagalli E,Funicello M,Rauen T,et al.Riluzole enhances the activity of glutamate transporters GLAST,GLT1 and EAAC1[J].Eur J Pharmacol,2008,578(2-3):171-176.
[33]Toklu HZ,Uysal MK,Kabasakal L,et al.The effects of riluzole on neurological,brain biochemical,and histological changes in early and late term of sepsis in rats[J].J Surg Res,2009,152(2):238-248.
[34]Chen WQ,Jin H,Nguyen M,et al.Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons[J].J Neurosci Res,2001,66(4):612-619.
[35]Zafarullah M,Li WQ,Sylvester J,et al.Molecular mechanisms of N-acetylcysteine actions[J].Cell Mol Life Sci,2003,60(1):6-20.
[36]Gegelashvili G,Schousboe A.High affinity glutamate transporters:regulation of expression and activity[J].Mol Pharmacol,1997,52(1):6-15.
[37]Danbolt NC.Glutamate uptake[J].Prog Neurobiol,2001,65(1):1-105.
[38]Xu B,Xu ZF,Deng Y,et al.Protective effects of MK-801 on methylmercury-induced neuronal injury in rat cerebral cortex:involvement of oxidative stress and glutamate metabolism dysfunction[J].Toxicology,2012,300(3):112-120.
[39]Xu B,Xu ZF,Deng Y,et al.MK-801 protects against intracellular Ca2+overloading and improves N-methyl-D-aspartate receptor expression in cerebral cortex of methylmercury-poisoned rats[J].J Mol Neurosci,2013,49(1):162-171.
[40]Liu W,Xu Z,Deng Y,et al.Protective effects of memantine against methylmercury-induced glutamate dyshomeostasis and oxidative stress in rat cerebral cortex[J].Neurotox Res,2013,24(3):320-337.
[41]Liu W,Xu Z,Yang T,et al.Memantine,a low-affinity NMDAreceptor antagonist,protects against methylmercury-induced cytotoxicity of rat primary cultured cortical neurons,involvement of Ca2+dyshomeostasis antagonism,and indirect antioxidation effects[J].Mol Neurobiol,2017,54(7):5034-5050.
[42]Feng S,Xu Z,Liu W,et al.Preventive effects of dextromethorphan on methylmercury-induced glutamate dyshomeostasis and oxidative damage in rat cerebral cortex[J].Biol Trace Elem Res,2014,159(1-3):332-345.
[43]Xu Z,Jia K,Xu B,et al.Effects of MK-801,taurine and dextromethorphan on neurotoxicity caused by manganese in rats[J].Toxicol Ind Health,2010,26(1):55-60.
[44]Deng Y,Xu Z,Liu W,et al.Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex[J].Oxid Med Cell Longev,2012,2012:534705.
[45]Deng Y,Xu Z,Xu B,et al.Exploring cross-talk between oxidative damage and excitotoxicity and the effects of riluzole in the rat cortex after exposure to methylmercury[J].Neurotox Res,2014,26(1):40-51.
[46]李乐慧,徐兆发,奉姝,等.牛磺酸对甲基汞染毒大鼠脑皮质Nrf2及HO-1、γ-GCS、GPx-1表达的影响[J].中国工业医学杂志,2013,26(3):163-166.
[47]李乐慧,徐兆发,刘巍,等.牛磺酸对甲基汞致大鼠脑谷氨酸代谢转运障碍的保护作用[J].实用预防医学,2014,21(3):261-263.
[48]李乐慧,徐兆发,刘巍,等.牛磺酸对甲基汞致大鼠脑氧化损伤的保护作用[J].环境与职业医学,2014,31(6):469-471,475.
[49]魏衍刚,徐兆发,邓宇,等.N-乙酰半胱氨酸对甲基汞致大鼠脑皮质氧化损伤和谷氨酸代谢障碍的影响[J].毒理学杂志,2012,26(2):79-83.
[50]魏衍刚,徐兆发,徐斌,等.N-乙酰半胱氨酸对甲基汞致大鼠脑皮质氧化损伤的影响[J].环境与健康杂志,2013,30(3):193-197,283.
[51]Yang TY,Xu ZF,Liu W,et al.Alpha-lipoic acid protects against methylmercury-induced neurotoxic effects via inhibition of oxidative stress in rat cerebral cortex[J].Environ Toxicol Pharmacol,2015,39(1):157-166.
[52]Yang T,Xu Z,Liu W,et al.Protective effects of alpha-lipoic acid on MeHg-induced oxidative damage and intracellular Ca2+dyshomeostasis in primary cultured neurons[J].Free Radic Res,2016,50(5):542-556.
[53]Yang T,Xu Z,Liu W,et al.Alpha-lipoic acid reduces ethylmercury-induced neuronal injury in rat cerebral cortex via antioxidation pathways[J].Environ Toxicol,2017,32(3):931-943.
[54]Liu W,Xu Z,Deng Y,et al.Excitotoxicity and oxidative damages induced by methylmercury in rat cerebral cortex and the protective effects of tea polyphenols[J].Environ Toxicol,2014,29(3):269-283.
[55]Liu W,Xu Z,Yang T,et al.The protective role of tea polyphenols against methylmercury-induced neurotoxic effects in rat cerebral cortex via inhibition of oxidative stress[J].Free Radic Res,2014,48(8):849-863.
[56]Liu W,Xu Z,Yang T,et al.Tea polyphenols protect against methylmercury-induced cell injury in rat primary cultured astrocytes,involvement of oxidative stress and glutamate uptake/metabolism disorders[J].Mol Neurobiol,2016,53(5):2995-3009.
[57]Yang H,Xu Z,Liu W,et al.Effect of grape seed proanthocyanidin extracts on methylmercury-induced neurotoxicity in rats[J].Biol Trace Elem Res,2012,147(1-3):156-164.
[58]Feng S,Xu Z,Wang F,et al.Sulforaphane prevents methylmercury-induced oxidative damage and excitotoxicity through activation of the Nrf2-ARE pathway[J].Mol Neurobiol,2017,54(1):357-391.
[59]奉姝,徐兆发,王飞,等.莱菔硫烷与右美沙芬联合应用对甲基汞致大鼠神经毒性的影响[J].环境与健康杂志,2015,32(8):663-667.
[60]徐兆发,奉姝,王飞,等.SFN和CUR对甲基汞致大鼠脑谷氨酸代谢转运及氧化损伤的影响[A]//中国环境科学学会.2016年中国环境科学学会学术年会论文集[C].海口:中国环境科学学会,2016:4287-4291.2018-12-12