有机磷化合物的胆碱酯酶动力学研究进展  

Advances in kinetics of organophosphorus compounds towards cholinesterase

作　　者：李克新 刘艳芹 刘玉龙 郭磊 谢剑炜 LI Ke-xin;LIU Yan-qin;LIU Yu-long;GUO Lei;XIE Jian-wei(State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2021年第12期949-961,共13页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点研发计划(2018YFC02600)。

摘　　要：有机磷化合物(OP)是在磷(膦)骨架上形成的复杂多样的结构,部分具有剧毒和高毒性。如军用制式神经性毒剂(NA)和有机磷农药等,对人类健康和生命造成了严重威胁。OP的胆碱酯酶(ChE)动力学研究是其毒性机制和抗毒药物研究的重要基础。本文在文献计量聚类分析的基础上,主要针对NA和部分有机磷农药,论述了OP抑制ChE的反应机制和胆碱酯酶动力学研究方法,重点总结了不同结构OP和不同种属ChE的动力学特征,特别针对OP对人ChE的抑制、老化与自发重活化动力学特征与模型、肟类重活化剂的重活化动力学特征和新型重活化剂的研究等进行综述,以期为全面了解OP毒性及其毒性特征、有效评估解毒剂和开发更有效的治疗方案等提供有益参考。Organophosphorus compounds(OPs) form complex and diverse structures on their organophosphorus or organophosphonate backbone.Some OPs,such as military nerve agents(NA)and organophosphorus pesticides,pose a great threat to human health and lives due to their acute or high toxicities.The kinetic research of OPs towards target cholinesterases is critical to the research on the toxicological mechanism of OPs and corresponding antidotes development.Based on bibliometric cluster analysis,this review outlines the reaction mechanism of OPs against cholinesterase,and research methods on kinetics parameters towards NA and some organophosphorus pesticides.This paper also summarizes the kinetic features attributed by OPs with different structures and cholinesterase with different species in general,and the kinetic parameters of inhibition,aging and spontaneous reactivation of OPs versus human cholinesterase,kinetic models,the reactivation kinetic characteristics of oxime reactivators,and the development of types reactivators in particular.It is expected to advance our understanding of the toxicities and toxicological property of OPs,effective evaluation of antidotes,and the development of more efficient treatment regimens.

关 键 词：有机磷化合物 神经性毒剂 胆碱酯酶 酶动力学 重活化剂 

分 类 号：R996[医药卫生—毒理学] R994.6[医药卫生—药学]