NEUROCHEMICAL STUDIES ON CNS DISTURBANCE CAUSED BY ORGANIC SOL VENTS

有机溶剂引起的中枢神经系统紊乱的神经化学研究

• 批准号: 02454200
• 负责人: TAKEUCHI Yasuhiro
• 金额: $ 4.22万
• 依托单位: NAGOYA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454200/
• 关键词: ORGANIC SOLVENT; TOLUENE; n-HEXANE,; MEK; CNS DISTURBANCE; NEURONAL AND GLIAL CELL MARKER PROTEINS; MICRODIALYSIS; DOPAMIN; メチルエチルケトン; 中枢神経毒性; 神経特異蛋白; 神経伝達物質

The mechanism of the CNS disturbance caused by organic solvents are studied in the animal experiments using neuronal and glial cell marker proteins as indicators in order to gain some basic data for early diagnosis and hygienic standard of organic solvent poisoning. The summary of the results is as follows;(1) In the subacute toluene exposure, rats were exposed to toluene 300,1000,3000 ppm,8 hours a day, 6 days a week,for 2 weeks. After the exposure, neuronal marker protein (gamma-enolase) and glial cell marker proteins (alpha-enolase,beta-100 protein, creatinekinase-B) were measured. The alpha-enolase and alpha- enolase significantly increased in the cerebellum and beta-100 protein significantly increased in the brainstem.(2) In the chronic toluene exposure, rats were exposed to 100,300,1000 ppm, 8 hours a day, 6 days a week, for 16 weeks. The glial cell marker proteins dose-dependently significaqntly increased in the cerebellum. The beta-100 protein significaqntly increased in the br … More ainstem and spinal cord. (3) In the chronic n-hexane exposure, In the subacute methylethylketone(MEK) exposure,rats were exposed to MEK 200,630,2000 ppm, 8 hours a day, 6 days a week, for 2 weeks. rats were exposed to n-hexane 2000 ppm, 12 hours a day, 6 days a week, for 24 weeks. The neuronal and glial cell marker proteins significaqntly decreased in the distal sciatic nerve. But these marker proteins did not significantly change in the CNS. The resuls suggest that these markers could be good indicators of the effects of organic solvents on the CNS, and toluene and MEK might cause gliosis in the CNS. (5) Rats were injected intraperitoneally with toluene 80,250,800 mg/kg and metaamphetamine. Dopamine and its metabolites DOPA and HVA in the striatum of the brain were measured by using microdialysis method. The behavior of the rats were observed. The dopamine and its metabolites, and behavior significantly increased in amphetamine group. The behavior significantly increased but dopamine and its metabolites did not change in toluene 800 mg/kg group. The results suggest that the mechanism of the effect of toluene could be different from that of amphetamine, and toluene might affect other portions of the brain. Less

通过动物实验，以神经元和神经胶质细胞标志物蛋白为指标，对有机溶剂中毒的中枢神经系统功能障碍的机制进行了研究，为有机溶剂中毒的早期诊断和卫生标准提供基础数据。结果如下：(1)在亚急性甲苯暴露中，大鼠暴露于甲苯300、1000、3000ppm，每天8小时，每周6天，共2周。暴露后检测神经元标志蛋白(伽马烯醇化酶)和胶质细胞标志蛋白(α-烯醇化酶、β-100蛋白、肌酸激酶-B)。小脑中α-烯醇酶和α-烯醇化酶显著升高，脑干中β-100蛋白显著增加。(2)在慢性甲苯暴露中，大鼠暴露于100,300,1000ppm，每天8小时，每周6天，共16周。小脑内胶质细胞标志蛋白呈剂量依赖性显著增加。Br…中的β-100蛋白显著增加更多的器官和脊髓。(3)慢性正己烷暴露、亚急性甲基乙基酮(MEK)暴露，染毒剂量分别为200、630、2000ppm，每周6天，每天8小时，共暴露2周。大鼠暴露在2000ppm的正己烷中，每天12小时，每周6天，持续24周。坐骨神经远端神经元和神经胶质细胞标志物蛋白明显减少。但这些标记蛋白在中枢神经系统中没有明显变化。结果提示，这些标志物可以很好地反映有机溶剂对中枢神经系统的影响，甲苯和MEK可能引起中枢神经系统的胶质细胞增厚。(5)大鼠腹腔注射甲苯80、250、800 mg/kg和偏苯丙胺。用微透析法测定脑纹状体多巴胺及其代谢物DOPA和HVA的含量。观察大鼠的行为变化。苯丙胺组大鼠多巴胺及其代谢物、行为明显增加。甲苯800 mg/kg组小鼠行为明显增加，但多巴胺及其代谢物无明显变化。结果提示，甲苯的作用机制可能与苯丙胺不同，甲苯可能影响大脑的其他部位。较少

项目成果

Shibata E.: "Changes in urinary n-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixed n-hexane levels." Arch Toxicol. 64. 168 (1990)

Shibata E.：“通过同时暴露于不同浓度的甲基乙基酮和固定的正己烷水平，尿液正己烷代谢物发生变化。”

SHIBATA,E.: "EFFECTS OF MEK ON KINETICS OF NーHEXANE METABOLITES IN SERUM." ARCH.TOXICOL.64. 247-250 (1990)

Shibata, E.：“MEK 对血清中正己烷代谢物动力学的影响。” ARCH.TOXICOL.64 (1990)。

Huang J.: "Dose dependent effects of chronic exposure to toluene on neuronal and glial cell marker proteins in the central nervous system of rats." Brit J Ind Med. 49. 282-286 (1992)

Huang J.：“长期接触甲苯对大鼠中枢神经系统神经元和神经胶质细胞标记蛋白的剂量依赖性影响。”

SHIBATA,E.: "CHANGES IN URINARY N-HEXANE METABOLITES BY CO-EXPOSURE TO VARIOUS CONCENTRATIONS OF METHYL ETHYL KETONE AND FIXED N-HEXANE LEVELS." ARCH TOXICOL. 64. 165-8 (1990)

Shibata,E.：“通过同时暴露于不同浓度的甲基乙基酮和固定的正己烷水平，尿液正己烷代谢物发生变化。”

SAITO,I.: "A STUDY ON URINARY 2,5ーHEXANEDIONE AS AN INDEX OF NーHEXANE EXPOSURE BY AN IMPROVED ANALYTICAL METHOD." BRIT.J.IND.MED.48. 568-574 (1991)

SAITO, I.：“通过改进的分析方法对尿液 2,5-己二酮作为正己烷暴露指标的研究。” BRIT.J.IND.MED.48 (1991)。