张宇童;杨兆娜;谢飞;马雪梅;王明连;

• 1:北京工业大学生命科学与生物工程学院

摘要(Abstract)：

有机磷农药是目前使用最为广泛的一种化学合成杀虫剂,它所引起的毒性作用已成为全球关注的公共卫生问题。研究表明,有机磷农药的神经发育毒性作用主要与其不可逆地抑制乙酰胆碱酯酶进而导致乙酰胆碱在突触处的积累有关。而最近也提出了有机磷农药的其他非胆碱酯酶作用机制,这些作用机制涉及兴奋性氨基酸递质系统、多巴胺能神经递质系统、五羟色胺递质系统、cAMP反应单元结合蛋白信号通路和氧化应激等。针对有机磷农药神经发育毒性作用机制的研究现状进行综述。

关键词(KeyWords)： 有机磷农药;神经发育毒性;胆碱酯酶;非胆碱酯酶

Abstract:

Keywords:

基金项目(Foundation): 公益性行业(农业)科研专项(201303023)

作者(Author): 张宇童;杨兆娜;谢飞;马雪梅;王明连;

Email:

DOI: 10.13989/j.cnki.0517-6611.2014.12.046

参考文献(References)：

• [1]BRADMAN A,BARR D B,HENN B G C,et al Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure:a validation study[J].Environ Health Perspect,2003,111(14):1779-1782.
• [2]WHYATT R M,CAMANN D,PERERA F P,et al.Biomarkers in assessing residential insecticide exposures during pregnancy and effects on fetal growth[J].Toxicol Appl Pharm,2005,206(2):246-254.
• [3]WHYATT R M,BARR D B.Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure:a validation study[J].Environ Health Perspect,2001,109(4):417-420.
• [4]ESKENAZI B,BRADMAN A,CASTORINA R.Exposures of children to organophosphate pesticides and their potential adverse health effects[J].Environ Health Perspect,1999,107(S3):409-419.
• [5]SLOTKIN T A,LEVIN E D,SEIDLER F J.Comparative Developmental Neurotoxicity of Organophosphate Insecticides:Effects on Brain Development Are Separable from Systemic Toxicity[J].Environ Health Perspect,2006,114(5):746-751.
• [6]COLBORN T.A Case for Revisiting the Safety of Pesticides:A Closer Look at Neurodevelopment[J].Environ Health Perspect,2006,114(1):10-17.
• [7]GUILLETTE E A,MEZA M M,AQUILAR M G,et al.An anthropological approach to the evaluation of preschool children exposed to pesticides in Mexico[J].Environ Health Perspect,1998,106(6):347-353.
• [8]ENGEL S M,BERKOWITZ G S,BARR D B,et al.Prenatal Organophosphate Metabolite and Organochlorine Levels and Performance on the Brazelton Neonatal Behavioral Assessment Scale in a Multiethnic Pregnancy Cohort[J].Am J Epidemiol,2007,165(12):1397-1404.
• [9]YOUNG J G,ESKENAZI B,GLADSTONE E A,et al.Association Between In Utero Organophosphate Pesticide Exposure and Abnormal Reflexes in Neonates[J].Neurotoxicology,2005,26(2):199-209.
• [10]GRANDJEAN P,HARARI R,BARR D B,et al.Pesticide Exposure and Stunting as Independent Predictors of Neurobehavioral Deficits in Ecuadorian School Children[J].American Academy of Pediatrics,2006,117(3):546-556.
• [11]周淑芳,沈莉,高宇,等.母鼠低剂量亚慢性暴露敌百虫对着床前期胚胎生长发育及细胞遗传学影响的研究[C]//二〇〇七年上海公共卫生国际研讨会.上海,2007:92-96.
• [12]陈伟峰.三种有机磷农药胚胎期暴露对发育期脑细胞组织结构的影响[D].杭州:浙江工业大学,2011.
• [13]SCHWAB B W,COSTA L G,MURPHY S D.Muscarinic receptor alterations as a mechanism of anticholinesterase tolerance[J].Toxicol Appl Pharm,1983,71(1):14-23.
• [14]FITZGERALD B B,COSTA L G.Modulation of M1 and M2 muscarinic receptor subtypes following repeated organophosphate exposure in rats[J].Toxicol Appl Pharm,1992,117(1):122-125.
• [15]CAADAS F,CARDONA D,DVILA E,et al.Long-Term Neurotoxicity of Chlorpyrifos:Spatial Learning Impairment on Repeated Acquisition in a Water Maze[J].Toxicological Sciences,2005,85(2):944-951.
• [16]PADILLA S,MARSHALL R S,HUNTER D L,et al.Neurochemical Effects of Chronic Dietary and Repeated High-Level Acute Exposure to Chlorpyrifos in Rats[J].Toxicol Sci,2005,88(1):161-171.
• [17]闫长会,檀德宏,彭双清.有机磷农药长期低剂量暴露致认知功能损伤的研究进展[J].中国药理学与毒理学杂志,2011,25(4):67-71.
• [18]郑捷,周志俊,张雪梅,等.慢性有机磷农药接触对羧基酯酶活力的影响[J].工业卫生与职业病,2005,31(2):68-71.
• [19]王青定,陈惠琼,李凤珍,等.Distribution of the scavenger esterases against organophosphorus compounds in human tissues[J].中国药理学与毒理学杂志,1998,12(2):91-93.
• [20]DOCHERTY M,BRADFORD H F,WU J Y.Co-release of glutamate and aspartate from cholinergic and GABAergic synaptosomes[J].Nature,1987,330(6143):64-66.
• [21]SHOAIB M,SCHINDLER C W,GOLDBERG S R,et al.Behavioural and biochemical adaptations to nicotine in rats:influence of MK801,an NMDA receptor antagonist[J].Psychopharmacology,1997,134(2):121-130.
• [22]SZIRKI I,SERSHEN H,BENUCK M,et al.Receptor systems participating in nicotine-specific effects[J].Neurochem Int,1998,33(5):445-457.
• [23]GIOVANNINI M G,RAKOVSKA A,DELLA CORTE L,et al.Activation of non-NMDA receptors stimulates acetylcholine and GABA release from dorsal hippocampus:a microdialysis study in the rat[J].Neurosci Lett,1998,243(1/3):152-156.
• [24]LEVIN E D,TIZABI Y,REZVANI A H,et al.Chronic nicotine and dizocilpine effects on regionally specific nicotinic and NMDA glutamate receptor binding[J].Brain Res,2005,1041(2):132-142.
• [25]JOHNSON E A,DAUGHERTY K S,GALLAGHER S J,et al.Glutamate receptor pathology is present in the hippocampus following repeated sublethal soman exposure in the absence of spatial memory deficits[J].Neurotoxicology,2008,29(1):73-80.
• [26]SHIH T,MCDONOUGH J H.Neurochemical Mechanisms in Soman-induced Seizures[J].J Appl Toxicol,1997,17(4):255-264.
• [27]吴强恩.兴奋性氨基酸递质系统在乐果神经毒性中的作用[D].上海:复旦大学,2007.
• [28]崔红梅.乐果对兴奋性氨基酸递质系统以及脑特异性蛋白的影响[D].上海:复旦大学,2010.
• [29]SLOTKIN T A,TATE C A,COUSINS M M,et al.Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure[J].Dev Brain Res,2002,133(2):163-173.
• [30]KAREN D J,LI W,HARP P R,et al.Striatal Dopaminergic Pathways as a Target for the Insecticides Permethrin and Chlorpyrifos[J].Neurotoxicology,2001,22(6):811-817.
• [31]OLANOW C W.The pathogenesis of cell death in Parkinson’s disease-2007[J].Movement Disord,2007,22(S17):335-342.
• [32]PRZEDBORSKI S.Pathogenesis of nigral cell death in Parkinson’s disease[J].Parkinsonism Relat D,2005,11(S1):3-7.
• [33]张洁.亚中毒阈剂量毒死蜱脑发育期暴露对大鼠黑质多巴胺能神经元的远期影响及机制[D].长沙:中南大学,2012.
• [34]SLOTKIN T A,LEVIN E D,SEIDLER F J.Developmental neurotoxicity of parathion:Progressive effects on serotonergic systems in adolescence and adulthood[J].Neurotoxicol Teratol,2009,31(1):11-17.
• [35]ALDRIDGE J E,MEYER A,SEIDLER F J,et al.Alterations in Central Nervous System Serotonergic and Dopaminergic Synaptic Activity in Adulthood after Prenatal or Neonatal Chlorpyrifos Exposure[J].Environ Health Perspect,2005,113(8):1027-1031.
• [36]SLOTKIN T A,SEIDLER F J.Comparative developmental neurotoxicity of organophosphates in vivo:Transcriptional responses of pathways for brain cell development,cell signaling,cytotoxicity and neurotransmitter systems[J].Brain Res Bull,2007,72(4/6):232-274.
• [37]SLOTKIN T A,RYDE I T,LEVIN E D,et al.Developmental neurotoxicity of low dose diazinon exposure of neonatal rats:Effects on serotonin systems in adolescence and adulthood[J].Brain Res Bull,2008,75(5):640-647.
• [38]SLOTKIN T A,SEIDLER F J.The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent[J].Dev Brain Res,2005,158(1/2):115-119.
• [39]RAINES K W,SEIDLER F J,SLOTKIN T A.Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos[J].Dev Brain Res,2001,130(1):65-72.
• [40]YAO D,RU S,KATOW H.The neurotoxic effects of monocrotophos on the formation of the serotonergic nervous system and swimming activity in the larvae of the sea urchin Hemicentrotus pulcherrimus[J].Environ Toxicol Phar,2010,30(2):181-187.
• [41]许磊.久效磷农药扰乱马粪海胆5-羟色胺能神经系统发育的机制研究[D].青岛:中国海洋大学,2012.
• [42]LIU R,FIORAVANTE D,SHAH S,et al.cAMP Response Element-Binding Protein 1 Feedback Loop Is Necessary for Consolidation of Long-Term Synaptic Facilitation in Aplysia[J].The Journal of Neuroscience,2008,28(8):1970-1976.
• [43]KELLY,LAROCHE S,DAVIS S.Activation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase in Hippocampal Circuitry Is Required for Consolidation and Reconsolidation of Recognition Memory[J].The Journal of Neuroscience,2003,23(12):5354-5360.
• [44]MAZZUCCHELLI C,VANTAGGIATO C,CIAMEI A,et al.Knockout of ERK1 MAP Kinase Enhances Synaptic Plasticity in the Striatum and Facilitates Striatal-Mediated Learning and Memory[J].Neuron,2002,34(5):807-820.
• [45]闫长会,焦利飞,赵君,等.毒死蜱低剂量重复染毒致学习记忆功能障碍及CREB信号途径的抑制[J].生态毒理学报,2010,5(6):823-828.
• [46]闫长会,焦利飞,赵君,等.毒死蜱致大鼠空间记忆损伤及ERK/CREB信号途径抑制[J].军事医学,2012,36(5):341-344.
• [47]GIORDANO G,AFSHARINEJAD Z,GUIZZETTI M,et al.Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency[J].Toxicol Appl Pharm,2007,219(2/3):181-189.
• [48]TUZMEN N,CANDAN N,KAYA E,et al.Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver[J].Cell Biochem Funct,2008,26(1):119-124.
• [49]OGUT S,GULTEKIN F,KISIOGLU A N,et al.Oxidative stress in the blood of farm workers following intensive pesticide exposure[J].Toxicol Ind Health,2011,27(9):820-825.
• [50]李鹏,尹雅玲,卢光洲,等.长期接触有机磷农药农民体内氧化应激水平的调查[J].工业卫生与职业病,2010,36(5):282-284.
• [51]AMBALI S,AYO J.Vitamin C Attenuates Chronic Chlorpyrifos-induced Alteration of Neurobehavioral Parameters in Wistar Rats[J].Toxicol Int,2012,19(2):144-152.
• [52]LU X,MA Y,WANG C,et al.Cytotoxicity and DNA damage of five organophosphorus pesticides mediated by oxidative stress in PC12 cells and protection by vitamin E[J].J Environ Sci Health B,2012,47(5):445-454.