[外周体液生化标志物在评估人类神经毒性中的作用]。

J Huang, H Tanii, K Hashimoto
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引用次数: 1

摘要

迄今为止,对化学诱导的人类神经毒性效应的评估主要依赖于电生理测量、神经行为测试和生物暴露评估。然而,最近已经尝试开发外周体液中的生化参数,这些参数可以很容易地从人身上获得,并且可以代表神经组织中相同参数的标记物。这种方法在逻辑上基于以下事实:1)血细胞(如血小板和淋巴细胞)具有单胺类神经元的一些特征,如存在单胺类储存囊泡、膜性神经递质受体、高亲和力摄取位点和神经递质相关代谢酶。2)靶神经元细胞或大分子损伤后,神经特异性标记物可能从神经组织渗漏到外周体液。3)当神经功能受到各种外源性或内源性因素的干扰时,周围生化标志物(如神经递质受体)可通过神经元、内分泌和免疫相互作用的调节机制引起定量和/或定性的改变。红细胞乙酰胆碱酯酶(AChE)、游离红细胞原卟啉(FEP)、淋巴细胞神经毒性靶酶(NTE)、血氨基乙酰丙酸脱水酶(ALA-D)和羧血红蛋白(CO-Hb)是众所周知的有机磷酸盐(AChE、NTE)、铅(FEP、ALA-D)和一氧化碳(CO-Hb)诱导作用的外周标志物。有机溶剂、重金属和农药对血液细胞神经传递参数(如神经递质摄取、受体结合和酶活性)的影响已有许多研究。本文综述了外周血中的神经传递参数、脑脊液、血液和尿液中的神经元或胶质细胞标记蛋白等外周生化标志物的研究进展及临床应用。本文还讨论了这些外周生化标志物在环境化学诱导的人类神经毒性评价中的作用。
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[The role of biochemical markers in peripheral body fluids in assessment of human neurotoxicity].

To date the evaluation of chemically-induced neurotoxic effects on humans has been dependent mostly on electrophysiological measurements, neurobehavioral tests and biological exposure assessment. However, recently attempts have been made to develop biochemical parameters in peripheral body fluids which can be easily obtained from humans and which can represent markers for the same parameters in nervous tissue. The approach of this kind is logically based on the following facts: 1) Blood cells (e.g., platelets and lymphocytes) possess some characteristics of monoaminergic neurons such as the existence of storage vesicles of monoamines, membrane neurotransmitter receptors, high affinity uptake sites and neurotransmitter-related metabolizing enzymes. 2) Leakage of nerve-specific markers from nervous tissue to peripheral body fluids may occur following damages of target neuronal cells or macromolecules. 3) Quantitative and/or qualitative alterations of peripheral biochemical markers (e.g. neurotransmitter receptors) can be induced by the regulation mechanisms of neuronal, endocrinal and immunologic interactions when the nervous functions are perturbed by various exogenous or endogenous factors. Erythrocyte acetyl cholinesterase (AChE), free erythrocyte protoporphyrin (FEP), lymphocyte neurotoxicity target enzyme (NTE), blood aminolevulinic acid dehydratase (ALA-D), and carboxyhemoglobin (CO-Hb) are well-known peripheral markers of the effects induced by organophosphates (AChE, NTE), lead (FEP, ALA-D) and carbon monoxide (CO-Hb). Many studies have been made on the effects of organic solvents, heavy metals and pesticides on neurotransmission parameters in blood cells such as neurotransmitter uptake, receptor binding and enzyme activity. This paper summarizes the present knowledge on the development and clinical applications of some peripheral biochemical markers such as neurotransmission parameters in blood cells and neuronal or glial cell marker proteins in CSF, blood and urine. The role of these peripheral biochemical markers in the assessment of environmental chemically-induced human neurotoxicity is also discussed.

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