纳米硫化铅和醋酸铅对大鼠脑组织氨基酸类神经递质影响研究
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摘要
目的探讨纳米硫化铅和醋酸铅亚慢性经口染毒对大鼠脑组织中谷氨酸(Glu)、丝氨酸(Ser)、甘氨酸(Gly)和γ-氨基丁酸(GABA)等氨基酸类神经递质的影响。方法无特定病原体级健康雌性SD大鼠随机分为对照组、醋酸铅组和纳米硫化铅组,每组15只。2个铅染毒组大鼠分别予给醋酸铅(100 mg/kg体质量)和纳米硫化铅混悬液(10 mg/kg体质量)灌胃,对照组予等体积质量分数为0.9%的氯化钠溶液灌胃,每周5次,连续12周。染毒结束处死大鼠,分离皮质和海马组织,采用电感耦合等离子体-质谱法测定铅水平,采用高效液相色谱法检测Glu、Ser、Gly和GABA水平。结果醋酸铅和纳米硫化铅组大鼠皮质、海马组织内的铅水平均分别高于对照组(P<0.05);纳米硫化铅组大鼠皮质和海马组织中的铅水平均低于醋酸铅组(P<0.05),分别为醋酸铅组的48.8%和54.0%。与对照组比较,醋酸铅组和纳米硫化铅组大鼠的皮质、海马组织中Glu水平均升高,GABA和Gly水平均下降(P<0.05);纳米硫化铅组大鼠皮质组织中Ser水平升高(P<0.05),而海马组织中Ser水平下降(P<0.05)。与醋酸铅组比较,纳米硫化铅组大鼠皮质组织中Glu和Ser水平均升高(P<0.05),海马组织中的GABA水平下降(P<0.05)。结论纳米硫化铅和醋酸铅暴露均可导致大鼠脑组织内氨基酸类神经递质水平改变;纳米硫化铅暴露的影响较醋酸铅更为明显,这可能是其发挥神经毒性的毒理学机制之一。
Objective To investigate the effect of subchronic orally exposure to nano-size lead sulfide and lead acetate on amino acid neurotransmitters such as glutamate( Glu),Serine( Ser),Glycine( Gly) and γ-aminobutyric acid( GABA)in rat brain tissues. Methods Specific pathogen free healthy female SD rats were randomly divided into the control group,lead acetate group and nano-size lead sulfide group,with 15 rats in each group. Rats in both lead exposure groups were given 100 mg / kg body weight( bw) lead acetate or nano-size lead sulfide particles at dose of 10 mg / kg bw by gavage. Rats in the control group were given the same amount of 0. 9%( mass fraction) sodium chloride solution. All rats were treated5 times per week for 12 continuous weeks. Rats were scarified 24 hours after the last time of lead exposure. The brain cortex and hippocampus were taken. The lead level was determined by inductively coupled plasma-mass spectrometry. High performance liquid chromatography was used to detect the levels of Glu,Ser,Gly and GABA. Results The lead levels in cortex and hippocampus of lead acetate and nano-size lead sulfide exposed groups were significantly higher than those of the control group( P < 0. 05). Meanwhile,lead levels in cortex and hippocampus of nano-size lead sulfide group were lower than those of lead acetate group( P < 0. 05),which were 48. 8% and 54. 0% of lead acetate group respectively. Compared with control group,the Glu levels in cortex and hippocampus of lead acetate group and nano-size lead sulfide group increased,and the levels of Gly and GABA decreased( P < 0. 05); the Ser level in cortex of nano-size lead sulfide group was increased( P < 0. 05),while the Ser level in hippocampus decreased( P < 0. 05). Compared with lead acetate group,the Glu and Ser levels in cortex were increased( P < 0. 05),and GABA level in hippocampus was decreased in nano-size lead sulfide group( P < 0. 05). Conclusion Both nano-size lead sulfide and lead acetate exposure can lead to the significant changes of brain neurotransmitter in rats. The more significant change was observed in nano-size lead sulfide exposed rats than in lead acetate ones,which might be one of the toxicology mechanisms of its inducing neurotoxicity.
Objective To investigate the effect of subchronic orally exposure to nano-size lead sulfide and lead acetate on amino acid neurotransmitters such as glutamate( Glu),Serine( Ser),Glycine( Gly) and γ-aminobutyric acid( GABA)in rat brain tissues. Methods Specific pathogen free healthy female SD rats were randomly divided into the control group,lead acetate group and nano-size lead sulfide group,with 15 rats in each group. Rats in both lead exposure groups were given 100 mg / kg body weight( bw) lead acetate or nano-size lead sulfide particles at dose of 10 mg / kg bw by gavage. Rats in the control group were given the same amount of 0. 9%( mass fraction) sodium chloride solution. All rats were treated5 times per week for 12 continuous weeks. Rats were scarified 24 hours after the last time of lead exposure. The brain cortex and hippocampus were taken. The lead level was determined by inductively coupled plasma-mass spectrometry. High performance liquid chromatography was used to detect the levels of Glu,Ser,Gly and GABA. Results The lead levels in cortex and hippocampus of lead acetate and nano-size lead sulfide exposed groups were significantly higher than those of the control group( P < 0. 05). Meanwhile,lead levels in cortex and hippocampus of nano-size lead sulfide group were lower than those of lead acetate group( P < 0. 05),which were 48. 8% and 54. 0% of lead acetate group respectively. Compared with control group,the Glu levels in cortex and hippocampus of lead acetate group and nano-size lead sulfide group increased,and the levels of Gly and GABA decreased( P < 0. 05); the Ser level in cortex of nano-size lead sulfide group was increased( P < 0. 05),while the Ser level in hippocampus decreased( P < 0. 05). Compared with lead acetate group,the Glu and Ser levels in cortex were increased( P < 0. 05),and GABA level in hippocampus was decreased in nano-size lead sulfide group( P < 0. 05). Conclusion Both nano-size lead sulfide and lead acetate exposure can lead to the significant changes of brain neurotransmitter in rats. The more significant change was observed in nano-size lead sulfide exposed rats than in lead acetate ones,which might be one of the toxicology mechanisms of its inducing neurotoxicity.
引文
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[22]李延海,王钰,张广军,等.D-丝氨酸对大鼠视皮层神经元突触后NMDA受体功能的调节作用[J].第四军医大学学报,2009,30(20):2098-2101.
[23]赵华颖,章劲夫.γ-氨基丁酸及其受体的研究进展[J].中华临床医师杂志:电子版,2012,6(14):4026-4028.
[24]Paine TA,Cooke EK,Lowes DC.Effects of chronic inhibition of GABA synthesis on attention and impulse control[J].Pharmacol Biochem Behav,2015,135:97-104.
[25]Wu Z,Guo Z,Gearing M,et al.Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer's disease model[J].Nat Commun,2014,5:4159.
[26]Zhang XY,Ji F,Wang N,et al.Glycine induces bidirectional modifications in N-methyl-D-aspartate receptor-mediated synaptic responses in hippocampal CA1 neurons[J].J Biol Chem,2014,289(45):31200-31211.
[2]Engstrom A,Wang H,Xia Z.Lead decreases cell survival,proliferation,and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases[J].Toxicol In Vitro,2015,29(5):1146-1155.
[3]Rao Barkur R,Bairy LK.Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development[J].Int J Occup Med Environ Health,2015,28(3):533-544.
[4]Liu KS,Hao JH,Zeng Y,et al.Neurotoxicity and biomarkers of lead exposure:a review[J].Chin Med Sci J,2013,28(3):178-188.
[5]Tozzi A.Information processing in the CNS:a supramolecular chemistry?[J].Cogn Neurodyn,2015,9(5):463-477.
[6]Watson DJ,Ostroff L,Cao G,et al.LTP enhances synaptogenesis in the developing hippocampus[J].Hippocampus,2015.doi:10.1002/hipo.22536.
[7]刘楠,徐厚军,李清钊,等.电感耦合等离子体质谱法测定纳米硫化铅染毒大鼠体内铅和铜[J].中国职业医学,2013,40(3):250-252.
[8]桂莉,田洪,郑健,等.高效液相色谱荧光法同时测定小鼠脑组织中4种氨基酸类神经递质[J].第三军医大学学报,2009,31(8):675-678.
[9]Ema M,Hougaard KS,Kishimoto A,et al.Reproductive and developmental toxicity of carbon-based nanomaterials:a literature review[J].Nanotoxicology,2015:1-22.
[10]梁丽红,黄振烈,黄汉林.纳米碳酸钙材料健康效应研究进展[J].中国职业医学,2014,41(2):211-213.
[11]Wang T,Guan RL,Liu MC,et al.Lead exposure impairs hippocampus related learning and memory by altering synaptic plasticity and morphology during juvenile period[J].Mol Neurobiol,2015:1-13.
[12]Cao Y,Liu H,Li Q,et al.Effect of lead sulfide nanoparticles exposure on calcium homeostasis in rat hippocampus neurons[J].J Inorg Biochem,2013,126:70-75.
[13]曹燕花.Nrf2/ARE信号通路在纳米硫化铅致大鼠学习记忆功能损害中的作用及机制研究[D].沈阳:中国医科大学,2013.
[14]尹镜雯,高晶,苏红,等.醋酸铅与纳米硫化铅经口染毒对仔鼠海马中氨基酸类神经递质的影响[J].毒理学杂志,2015,29(3):168-172.
[15]王苗苗,董亚楠,闫立成,等.铅暴露对大鼠血脑脊液屏障通透性、分泌及转运功能的影响[J].中国药理学与毒理学杂志,2014,4(28):188-193.
[16]Ross KA,Brenza TM,Binnebose AM,et al.Nano-enabled delivery of diverse payloads across complex biological barriers[J].J Control Release,2015.doi:10.1016/j.jconrel.2015.08.039.
[17]Feng X,Chen A,Zhang Y,et al.Central nervous system toxicity of metallic nanoparticles[J].Int J Nanomedicine,2015,10:4321-4340.
[18]Yang P,Li X,Ni J,et al.Alterations of amino Acid level in depressed rat brain[J].Korean J Physiol Pharmacol,2014,18(5):371-376.
[19]Wang H,Peng R,Zhao L,et al.The relationship between NMDA receptors and microwave-induced learning and memory impairment:a long-term observation on Wistar rats[J].Int J Radiat Biol,2015,91(3):262-269.
[20]李婧,孙建栋,苑玉和,等.谷氨酸能神经传递在抑郁症发病机制中作用的研究进展[J].神经药理学报,2014,4(1):20-24.
[21]Cheriyan J,Mezes C,Zhou N,et al.Heteromerization of ligand binding domains of N-methyl-D-aspartate receptor requires both coagonists,L-glutamate and glycine[J].Biochemistry,2015,54(3):787-794.
[22]李延海,王钰,张广军,等.D-丝氨酸对大鼠视皮层神经元突触后NMDA受体功能的调节作用[J].第四军医大学学报,2009,30(20):2098-2101.
[23]赵华颖,章劲夫.γ-氨基丁酸及其受体的研究进展[J].中华临床医师杂志:电子版,2012,6(14):4026-4028.
[24]Paine TA,Cooke EK,Lowes DC.Effects of chronic inhibition of GABA synthesis on attention and impulse control[J].Pharmacol Biochem Behav,2015,135:97-104.
[25]Wu Z,Guo Z,Gearing M,et al.Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer's disease model[J].Nat Commun,2014,5:4159.
[26]Zhang XY,Ji F,Wang N,et al.Glycine induces bidirectional modifications in N-methyl-D-aspartate receptor-mediated synaptic responses in hippocampal CA1 neurons[J].J Biol Chem,2014,289(45):31200-31211.