冀晓莹;高美丽;

• 1:生物科学工程实验室教育部生物信息工程重点实验室西安交通大学生命科学与技术学院

摘要(Abstract)：

苯并(a)芘(BaP)是一种广泛存在于环境中的多环芳烃,具有致癌、致畸、致突变性。目前BaP的神经毒性研究零散而不深入,本文主要总结分析了BaP的神经毒性表现,简要介绍了BaP诱发神经毒性呈现的剂量-效应关系,进一步系统阐述了目前研究中发现的可能分子机制,包括BaP诱导神经递质及其代谢物含量的改变,相关DNA及蛋白质的损伤,抗氧化系统及线粒体的改变等,以期为进一步研究提供参考。

关键词(KeyWords)： 苯并(a)芘;神经毒性;剂量-效应关系

Abstract:

Keywords:

基金项目(Foundation): 陕西省自然科学基金(2014JQ4136)

作者(Author): 冀晓莹;高美丽;

Email:

参考文献(References)：

• [1]Wormley D D,Ramesh A,Hood D B.Environmental contaminant-mixture effects on CNS development,plasticity,and behavior[J].Toxicology and Applied Pharmacology,2004,197(1):49-65
• [2]Zenz C,Dickerson O B,Horvath E P.Occupational Medicine[M].Mosby,St.Louis,M O,1994,928:75-76
• [3]Phillips D H.Fifty years of benzo[a]pyrene[J].Nature,1983,303:468-472
• [4]Nesnow S,Davis C,Nelson G B,et al.Comparison of the genotoxic activities of the K-region dihydrodiol of benzo[a]pyrene with benzo[a]pyrene in mammalian cells:Morphological cell transformation;DNA damage;and stable covalent DNA adducts[J].Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2002,521(1):91-102
• [5]Qiu C,Cheng S,Tu B,et al.Effects of subchronic benzo[a]pyrene exposure on neurotransmitter receptor gene expression in the rat hippocampus related with spatial learning and memory change[J].Toxicology,2011,289(2-3):83-90
• [6]唐倩,夏茵茵,涂白杰,等.苯并芘对大鼠记忆及谷氨酸盐受体基因表达影响[J].中国公共卫生,2011,27(7):902-903Tang Q,Xia Y Y,Tu B J,et al.Effect of benzo(a)pyrene on memory and expression of glutamate receptor m RNA in rat[J].Chinese Journal of Public Health,2011,27(7):902-903(in Chinese)
• [7]涂白杰,胡雪原,韩令力.苯并[a]芘、铅染毒小鼠神经毒性及脑组织细胞凋亡的研究[J].中国职业医学,2001,31(5):14-17Tu B J,Hu X Y,Han L L.Neurotoxicity and brain cell apoptosis induced by lead or/and benzo[a]pyrene in mice[J].China Occupational Medicine,2001,31(5):14-17(in Chinese)
• [8]袁海艳,汤艳,涂白杰,等.[14C]苯并[a]芘在SD大鼠纹状体的动态分布研究[J].重庆医科大学学报,2009,34(6):677-679Yuan H Y,Tang Y,Tu B J,et al.Study on the dynamic distribution of[14C]benzo(a)pyrene in the corpus striatum[J].Journal of Chongqing Medical University,2009,34(6):677-679(in Chinese)
• [9]Gao D X,Wu M F,Wang C G,et al.Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish(Danio rerio)[J].Aquatic Toxicology,2015,167:200-208
• [10]Kaiser J.Hormesis sipping from a poisoned chalice[J].Science,2003,302(564):376-379
• [11]Calabrese E J,Baldwin L A.Toxicology rethinks its central belief[J].Nature,2003,421(6924):691-692
• [12]Bouayed J,Bohn T,Tybl E,et al.Benzo[a]pyrene-induced anti-depressive-like behaviour in adult adult female mice:Role of monoaminergic systems[J].Basic&Clinical Pharmacology&Toxicology,2012,110(6):544-550
• [13]Grova N,Schroeder H,Farinelle S,et al.Sub-acute administration of benzo[a]pyrene(B[a]P)reduces anxietyrelated behaviour in adult mice and modulates regional expression of N-methyl-d-aspartate(NMDA)receptors genes in relevant brain regions[J].Chemosphere,2008,73(1):S295-S302
• [14]Dutta K,Ghosh D,Nazmi A,et al.A common carcinogen benzo[a]pyrene causes neuronal death in mouse via microglial activation[J].PLo S One,2010,5(4):9984
• [15]Aktay G,Emre M H,Polat A.Influence of dihydropyridine calcium antagonist nitrendipine on benzo[a]pyrene-induced oxidative stress[J].Archives of Pharmacal Research,2011,34(7):1171-1175
• [16]聂继盛,赵捷,牛侨,等.侧脑室注射苯并[a]芘对大鼠学习记忆功能和单胺类神经递质的影响[J].卫生研究,2008,37(5):517-520Nie J S,Zhao J,Niu Q,et al.Effects of benro(a)pyrene on learning and memory and the content of monoamine neurotransmitters in rats[J].Journal of Hygiene Research,2008,37(5):517-520(in Chinese)
• [17]程淑群,王应雄,涂白杰,等.苯并[a]芘对大鼠学习记忆能力及氨基酸类神经递质的影响[J].现代预防医学,2012,39(3):670-672Cheng S Q,Wang Y X,Tu B J,et al.Effect of benro(a)pyrene on learning and memory behaviors and the experession of aminoacid neuro transmitters in rats[J].Modern Preventive Medicine,2012,39(3):670-672(in Chinese)
• [18]郭亮.亚慢性染毒苯并[a]芘对大鼠胆碱能系统的影响[D].太原:山西医科大学,2012Guo L.Effect of subchronic benro(a)pyrene exposure on rat cholinergic systerm[D].Taiyuan:Shanxi Medical University,2012(in Chinese)
• [19]段蕾,阎智伟,聂继盛,等.慢性苯并[a]芘暴露对大鼠学习记忆及谷氨酸受体影响[J].中国公共卫生,2013,29(7):1004-1006Duan L,Yan Z W,Nie J S,et al.Effects of chronic benzo[a]pyrene exposure on learning and memory and metabotropic glutamate receptor in rats[J].Chinese Journal of Public Health,2013,29(7):1004-1006(in Chinese)
• [20]Patri M,Singh A,Mallick B N.Protective role of noradrenaline in benzo[a]pyrene-induced learning impairment in developing rat[J].Journal of Neuroscience Research,2013,91(11):1450-1462
• [21]程淑群,汤艳,涂白杰,等.苯并[a]芘对大鼠学习记忆行为及海马NOS和NO的影响[J].现代预防医学,2010,3(3):434-436Cheng S Q,Tang Y,Tu B J,et al.Effects of chronic benzo[a]pyrene on learning behaviors and NOS and NO in hippocampus of rats[J].Modern Preventive Medicine,2010,3(3):434-436(in Chinese)
• [22]Duan L,Tang Y,Tu B J,et al.Effects of benzo[a]pyrene exposure on oxidative stress and ATPase in the hippocampus of rats[J].Chinese Journal of Industrial Hygiene and Occupational Diseases,2013,31(7):500-503
• [23]涂白杰,彭斌.苯并[a]芘染毒致小鼠脑组织胞核DNA损伤[J].中国公共卫生,2006,22(1):82-83Tu B J,Peng B.Brain tissue DNA damage in benzo[a]pyrene-poisoned mice[J].Chinese Journal of Public Health,2006,22(1):82-83(in Chinese)
• [24]汤艳,陈承志,涂白杰,等.14C-苯并[a]芘在大鼠海马中的分布及对海马神经元的损害[J].环境与职业医学,2011,28(3):141-143Tang Y,Chen C Z,Tu B J,et al.Dynamic distribution of14C-benzo(a)pyrene and damage of neuron in hippocampus of rat[J].Journal of Environmental&Occupational Medicine,2011,28(3):141-143(in Chinese)
• [25]涂白杰,邬堂春,贺涵贞.苯并[a]芘对小鼠的神经毒性及脑组织热应激蛋白水平的影响[J].卫生研究,2004,33(1):15-17Tu B J,Wu T C,He H Z.Study on the neurotoxicity and brain tissue HSPs level in benzo[a]pyrene exposed mice[J].Journal of Hygiene Research,2004,33(1):15-17(in Chinese)
• [26]许国耀,郑金平.苯并[a]芘对体外培养大鼠皮层神经元HSP70表达的影响[J].卫生研究,2011,40(4):437-440Xu G Y,Zheng J P.Effect of benzo[a]pyrene on HSP70expression in rat cortical neurons in vitro[J].Journal of Hygiene Research,2011,40(4):437-440(in Chinese)
• [27]聂继盛,张红梅,邢景才,等.苯并[a]芘神经行为毒性与CYP1A1基因多态性的关系[J].环境与职业医学,2009,26(4):324-328Nie J S,Zhang H M,Xin J C,et al.Relationship betweenneurobehavioral toxicity of benzo(a)pyrene and CYP1A1gene polymorphism[J].Journal of Environmental&Occupational Medicine,2009,26(4):324-328(in Chinese)
• [28]魏建宏,张红梅,牛侨,等.苯并(a)芘对神经细胞的毒性及细胞色素P4501A1的诱导表达[J].解剖学报,2012,43(5):608-613Wei J H,Zhang H M,Niu Q,et al.Relationship between cytotoxicity of neural cell and CYP1A1 expression induced by benzo(a)pyrene[J].Acta Anatomica Sinica,2012,43(5):608-613(in Chinese)
• [29]Nie J,Duan L,Yan Z,et al.Tau hyperphosphorylation is associated with spatial learning and memory after exposure to benzo[a]pyrene in SD rats[J].Neurotoxicity Research,2013,24(4):461-471
• [30]阎智伟,段蕾,聂继盛.苯并[a]芘亚慢性染毒致大鼠学习记忆功能损伤Tau蛋白磷酸化改变[J].中国职业医学,2014,41(2):132-136Yan Z W,Duan L,Nie J.Effect of subchronic benzo[a]pyrene exposure on impairment of learning and memory abilities and expression of tau phosphorylation in rats[J].China Occupational Medicine,2014,41(2):132-136(in Chinese)
• [31]Zhao J,Wang L P,Nie J S,et al.Effects of benzo[a]pyrene on apoptosis of neuronal cells and expression of Bcl-2and Bax proteins in rat brain tissue[J].Chinese Journal of Industrial Hygiene and Occupational Diseases,2011,29(11):820-824
• [32]王晓燕,李娜,聂继盛,等.组蛋白乙酰化酶2基因在苯并[a]芘致神经细胞凋亡中的量效和时效表达[J].环境与职业医学,2011,28(4):219-223Wang X Y,Li N,Nie J S,et al.The dose-effect and time-effect expression of histone deacetylase 2 m RNA in B(a)P-induced neural cell apoptosis[J].Journal of Environmental&Occupational Medicine,2011,28(4):219-223(in Chinese)
• [33]Saunders C R,Das S K,Ramesh A,et al.Benzo[a]pyrene-induced acute neurotoxicity in the F-344 rat:Role of oxidative stress[J].Journal of Applied Toxicology,2006,26(5):427-438
• [34]南阿若,赖延东,蒋义国.苯并芘诱导细胞转化过程中PP2AB56ε表达与DNA损伤修复功能的研究[J].安徽医药,2014,18(11):2036-2039Nan A R,Lai Y D,Jiang Y G.PP2A B56εexpression and DNA damage repair during cell transformation induced by benzo(α)pyrene[J].Anhui Medical and Pharmaceutical Journal,2014,18(11):2036-2039(in Chinese)
• [35]聂继盛,刘慧君,牛侨,等.苯并[a]芘对神经元的细胞活性和脂质过氧化的影响[J].山西医科大学学报,2007,38(12):1060-1063Nie J S,Liu H J,Niu Q,et al.Effect of benzo(a)pyrene on viability and lipid peroxidation of neuron[J].Journal of Shanxi Medical University,2007,38(12):1060-1063(in Chinese)
• [36]Duan L,Tang Y,Tu B J,et al.Effects of benzo[a]pyrene exposure on oxidative stress and ATPase in the hippocampus of rats[J].Chinese Journal of Industrial Hygiene and Occupational Diseases,2013,31(7):500-503
• [37]Xia Y,Cheng S,Tu B,et al.Effects of subchronic exposure to benzo[a]pyrene(B[a]P)on learning and memory,and neurotransmitters in male Sprague-Dawley rat[J].Neuro Toxicology,2011,32(2):188-198
• [38]陈承志,汤艳,涂白杰,等.苯并[a]芘对大鼠学习记忆及海马神经元影响[J].中国公共卫生,2011,27(5):608-610Chen C Z,Tang Y,Tu B J,et al.Morphology in hippocam palneurons and behavioral change in rats with subchronic exposure of benzo(a)pyrene[J].Chinese Journal of Public Health,2011,27(5):608-610(in Chinese)
• [39]Nie J S,Zhao J,Liu H J,et al.Changes of mitochondria membrane potential and cytoplasmic cytochrome C in neuron apoptosis induced by benzo[a]pyrene[J].Chinese Journal of Industrial Hygiene and Occupational Diseases,2010,28(1):8-11
• [40]Nie J S,Zhang H M,Zhao J,et al.Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis[J].Human&Experimental Toxicology,2014,33(3):240-250
• [41]Schellenberger M T,Grova N,Farinelle S,et al.Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P-diphtheria toxoid conjugate[J].Toxicology and Applied Pharmacology,2013,271(272):175-283