【作者】 任振华；

【导师】 李光武；

【作者基本信息】 安徽医科大学 ， 神经生物学， 2005， 硕士

【摘要】 研究背景及研究目的 甲苯(toluene,Tolu)是芳香烃类化合物,主要来自于石油的催化重整。主要用作汽油的添加成分,以提高汽油的辛烷值,以及作为化工原料用于生产苯、二甲苯等。另外,甲苯是一种优良的作有机溶剂,被广泛应用于涂料、胶粘剂、油墨、油漆等行业。随着工业的发展,甲苯消耗量的逐步增加,甲苯的接触人群日益增多,其职业危害及环境污染也正逐年增加。 甲苯具有很强的挥发性及脂溶性,易透过血脑屏障,对中枢神经系统具有很强的毒性作用。流行病学调查表明接触人群有明显的神经功能障碍。急性甲苯中毒可引起急性中毒性脑病、脑水肿,出现不同程度的意识及精神障碍。长期吸入甲苯,可引起神经行为功能紊乱,导致弥漫性小脑萎缩,出现精神疾病、痴呆甚至死亡。 虽然甲苯的神经毒性很早就引起人们的关注,但其神经毒性的研究仍停留在环境流行病学和回顾性调查,神经毒性机制国内外很少涉及,对于其引起的神经毒性损伤的防治更少涉及。本研究的目的在于认识甲苯的神经毒性机制,提高人们对甲苯危害的认识,从而控制或减少甲苯的使用,为降低其危害提供理论依据。 吸入或腹腔注射甲苯容易引起其他脏器如肝、肾等的损伤,从而影响或掩盖其神经毒性。因此,本实验通过脑立体定位装置定点向小鼠脑室内注射甲苯的方法来建立甲苯中毒模型,观测其神经行为学及中枢神经系统形态学的变化,对甲苯的神经毒性作用及其机制进行研究。 第一部分 神经毒性物质的小鼠神经行为学比较 材料与方法 为比较神经毒性物质的毒性强弱,选择了中枢神经系统毒性物质5种,包括金属离子2种(醋酸铅、三氯化铝),抗精神病药物2种(碳酸锂、苯妥英钠),有机溶剂1种(甲苯)。应用神经行为学的方法,观测小鼠自主活动及学习记忆能更多还原

【Abstract】 Background and Objective of researchToluene is one of Aromatic hydrocarbon, mainly produced by catalytic reforming of petroleum. As the affixture of gasoline, toluene is used to raise the gasoline octane value. As chemical materials it is mainly used to produce benzene and xylenes, on the other hand, it also can be widely used as organic solvent in coating, adhesive, printing ink and paint. Along with the development of industry, and the consume of toluene is increasing gradually, there are more people working with toluene, the occupational disease and pollution of the environment due to toluene also is increasing.Toluene has very strong volatility and liposolubility. Therefore, toluene permeate through the blood-brain barrier easily, and having the very strong toxicity function to the central nervous system. Epidemiology investigates to express that the crowd contacted with toluene may induce obvious nervous obstacle. Acute poisoning of toluene can cause acute toxic encephalopathy, brain edema, and appear conscious disturbance and mental disorder of different degree. With long-term inhalation of high density toluene occupationally, can cause the nerve behavior functional disorder. Inhaling toluene over long time, can cause cerebellar atrophy dispersedly, appear the mental disease, dementia even death.Neurotoxic effect of toluene have been concerned for a long time, but the research of its neurotoxicity is staying on the investigation and environment epidemiology and reviews only, its mechanism were seldom researched in abroad and domestic, the research, which prevent and cure toluene neurotoxicity, is rarely.The purpose of this research would provide the theoretical evidence.in order to clarify the mechanism of toluene neurotoxicity, and raise the people to understand the detriment of toluene, thus control or reduce the usage of toluene, thereby decrease itshazardous. In our experiment, the model of toluene neurotoxicity was established through the stereotaxis instrument by which injected toluene into mouse brain intraventricular, through observing the change of neurobehavior and nervous morphology, to investigate the effect of its neurotoxicity and its mechanisms of toluene.Part one. Comparison study of neurotoxic material on the mouse neurobehaviorMaterials and methodsIn order to clartify that the toxicity of neurotoxic material is strong or weak, we have chosen neurotoxic material 5 kinds, include metals 2 kinds (Plumb and Aluminium), anti-mental illness medicine 2 species (Lithium Carbonate and Phenytoin), organic solvent is 1 kind (Toluene). By investigate the influence of neurotoxic material upon the mouse ability of study and memory and autonomic activities, to compare the mouse neurobehavioral toxicity of neurotoxic material. ResultsLook through the mouse neurotixic results of neurotoxic materials, founding that toluene and lead acetate have obvious influence to the mouse study memory ability, and the effect of both is reversible. Carry on the comparison with the saline set and the sham operation set; toluene did not affect autonomic activities of the mouse obviously.Part two. The study of toluen neurotoxicity on the mouse by neurobehaviorMaterials and methodsBase on above-mentioned result, according to same experiment method mentioned before, to study the time-effect and dose-effect relationship of 1 u 1 dose set(call as follows low dose) and 2.5 u 1 dose set(call as follows high dose)on toluene neurotoxicity, and more detailed to illuminate the influence of toluene on the mouse study and memory and autonomic activities. ResultsThe influence of low dose toluene to the ability of study and memory is temporal and reversible, recover to normal after 3 weeks. But the influence of high dose toluene is very significant, and last for long time. The number of autonomic activities raise obviously in high dose toluene in 3d and 5d.Part three. The study of toluene nervous morphological neurotoxicity on the mouse by immunohistochemistryMaterials and methodsThe result of neurobehavior hint that toluene can decrease the mouse abilities of study and memory. In order to investigate the relation of the change of neurobehavior and neurotransimitter, using of immunochemistry method to research the time-effect of different dose of toluene to neurotransimitter in the mouse brain, to inquiry into the neurotoxicity mechanism of toluene. ResultsCHAT positive cells mainly distributes in cerebral cortex, hippocampus and nucleus. Contrasted with controls, the number of CHAT positive cells has no obvious change in low dose toluene, but in high dose toluene positive cells reduces obviously, after 3w in front cortex, posterior cingulated cortex and hippocampus already recover normally. In cerebellum positive cells mainly distribute in the nucleus inside medulla of cerebellum and brainstem, in cerebellum cortex have no positive cell.GABA positive cells mainly distributes in cortex, hippocampus and nucleus, in caudate putamen has no positive cells. In cortex and hippocampus, the number of GABA positive cells of low dose decrease lightly, but reduce obviously in high dose after 2w. In cerebellum positive cells mainly distributes in nucleus inside brainstem, contrast with contral, positive cells increase lightly in low dose, but reduce obviously in high dose after 2w.Glu positive cells mainly distributes in white matter and nucleus, hippocampus and更多还原