高等学校化学学报2017，Vol.38Issue(5)：758-763,6.DOI:10.7503/cjcu20160945
膦酰化肟对乙酰胆碱酯酶的抑制作用及中毒酶重活化特性研究——基于效应标志物质谱定量分析技术
Studies on Poisoning Characteristics of Phosphylated Oxime on AChE and Efficacy of Reactivators Based on Quantitative Determination of Effect Biomarkers by Liquid Chromatograph-mass Spectrometry
摘要
Abstract
Organophosphorus compounds(OPs) have been extensively utilized throughout the world for many years, however, the security problems are always concerned due to the high toxicity.OPs primarily inhibit acetylcholinesterase(AChE) in nerve system and will cause cholinergic crisis in the synaptic cleft.Enzyme reactivatorsd representing oxime derivatives of quarternary pyridinium compounds are considered as specific medications.Recently, the exact clinical effectiveness of oxime reactivators is a matter of controversy.Although oxime reactivators can recover the activity of AChE and improve neuromuscular transmission, some study reports found oximes could also react with OPs and formmore potent inhibitors of AChE during the process of reactivation, which may intoxicate the reactivated AChE once again, even worsen the poisoning of enzyme due to the high reactivity.In this paper, paraoxon as an example of OPs and obidoxime representing a typical oxime were chosen to demonstrate the reactivation efficacy of oximes in the treatment of OPs poisoning.The reaction product diethylphosphoryl obidoxime(DEP-obidoxime) was first prepared.Then, the poisoning characteristics of phosphylated oxime on AChE and efficacy of reactivators were studied via quantitative determination of the effect biomarkers formed between paraoxon and AChE.The experimental results confirmed that DEP-obidoxime can intoxicate AChE in extremely short time, fortunately, the poisoned AChE by DEP-obidoxime can still be reactivated by typical oximes[pralidoxime, pyramidoxime monohydrate(HI-6) and obidoxime].EC50 values of each oxime were determined and indicated that the reactivation effectiveness of the above oximes as the following ranking: pralidoxime>HI-6>obidoxime.关键词
有机磷农药/肟类化合物/膦酰化肟/生物标志物/液相色谱-质谱联用Key words
Organophosphorus compound/Oxime/Phosphoryl oxime/Biomarker/Liquid chromatograph-mass spectrometry(LC-MS)分类
化学化工引用本文复制引用
谢琰,陈佳,徐斌,闫珑,唐吉军,谢剑炜..膦酰化肟对乙酰胆碱酯酶的抑制作用及中毒酶重活化特性研究——基于效应标志物质谱定量分析技术[J].高等学校化学学报,2017,38(5):758-763,6.基金项目
国家自然科学基金(批准号:81202248,81302473)资助.Supported by the National Natural Science Foundation of China(Nos.81202248,81302473). （批准号:81202248,81302473）
