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环境毒物所致周围神经病的动物模型

Animal models of peripheral neuropathy due to environmental toxicants.

作者信息

Rao Deepa B, Jortner Bernard S, Sills Robert C

出版信息

ILAR J. 2014;54(3):315-23. doi: 10.1093/ilar/ilt058.

Abstract

Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves.

摘要

尽管我们对周围神经病变的发病机制和病因识别有了进展,但特发性神经病变仍然很常见。通常,相对于更常见的周围神经病变病因(糖尿病和化疗药物),对因接触环境因素导致的周围神经病变的关注较少。鉴于美国环境保护局登记的商业化学品有8万多种,且已知至少1000种化学品具有神经毒性潜力,但只有极少数化学品被证实会影响周围神经系统(主要是职业接触后)。从历史到近期,各种各样的接触,包括农药、金属、溶剂、营养源和药剂,都与环境毒物引起的周围神经病变有关。文献综述表明,已使用动物模型研究了对周围神经系统产生不利影响的化学品的毒性和发病机制。本文概述了已知会导致周围神经病变的五种典型环境因素,即有机磷、二硫化碳、吡哆醇(维生素B6)、丙烯酰胺和六碳化合物(主要是正己烷、2,5 -己二酮、甲基正丁基酮)。还简要介绍了周围神经系统的结构组成以及周围神经组织病理学评估的常用方法要点。

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