三氯乙烯与帕金森病.PDF

中国临床神经科学 2013年第 21卷第2期 182 Chin J Clin Neurosci 2013,21 (2),182~187 疾病的新认识和新治疗 三氯乙烯与帕金森病 刘疏影，王 坚 (复旦大学附属华山医院神经科200040) 关键词 三氯乙烯；帕金森病；环境污染；1-三氯甲基-1, 2, 3, 4-四氢化-b -咔啉 摘要 三氯乙烯(TCE)是一种常用工业溶剂，具有高度挥发性和脂溶性，广泛存在于环境中。近期流行病学证据表明， 接触TCE 可能导致帕金森病(PD) 。其机制与抑制线粒体酶活性、氧化应激、炎性反应途径和诱导-synuclein 聚集引起 黑质纹状体多巴胺能神经元损伤相关。TCE 下游代谢物三氯乙醛可在体内与色胺结合产生1- 甲基-4- 苯基1, 2, 3, 6- 四 氢吡啶(MPTP)类似物1- 三氯甲基-1, 2, 3, 4- 四氢化-- 咔啉(TaClo)特异性抑制线粒体复合体Ⅰ导致多巴胺能神经元受 损。本文就TCE 的一般性质、体内代谢过程、与PD 发病的关系、可能机制、目前研究中的问题进行总结和展望。 Trichloroethylene and Parkinson ’s Disease LI U Shu-y ing, WAN G J ian Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China KEY WORD trichloroethylene; Parkinson ’s disease; environmental pollution; 1-trichloromethyl- 1, 2, 3, 4-tetrvahydro-b-carboline ABSTRACT Trichloroethylene(TCE) is a widely-used industry solvent which has strong volatility and solubility and is ubiquitous in the environment. The epidemiology evidence showed that ever exposure to TCE may be associated with significantly increased risk of Parkinson ’s disease (PD). TCE can selectively cause dopaminergic neurodegeneration, which may be mediated by mitochondrial dysfunction, inflammation, oxidative stress and gathering of -synuclein. In the mean time, trichloroacetaldehyde, one of the metabolites of TCE, can be combined with tryptamine in human body. The reaction forms a new chemical substance, 1-trichloromethyl- 1, 2, 3, 4-tetrvahydro--carboline(TaClo), which is similar with MPTP in structure. TaClo has the ability to inhibit mitochondria complex 1 and cause damage to dopaminergic neurons. In summary, TCE may have strong relationship with the development of PD and the mechanism is still under exploration. 帕金森病(Parkinson ’s disea