共同滥用条件下乙醇对吗啡肝脏内代谢影响的研究  

Effect of alcohol on morphine metabolism in the liver under the condition of combined abuse

作　　者：崔胜峰 张娜[1] 王腾 周成合 万敬伟 CUI Sheng-Feng;ZHANG Na;WANG Teng;ZHOU Cheng-He;WAN Jing-Wei(Zhengzhou Key Laboratory of Criminal Science and Technology,Department of Criminal Science and Technology,Railway Police College,Zhengzhou 450053,China;Institute of Public Safety,Zhengzhou University,Zhengzhou 450001,China;Key Laboratory of Applied Chemistry of Chongqing Municipality,Institute of Bioorganic&Medicinal Chemistry,School of Chemistry and Chemical Engineering,Southwest University,Chongqing 400715,China)

机构地区：[1]铁道警察学院刑事科学技术系,郑州市刑事科学技术重点实验室,河南郑州450053 [2]郑州大学公共安全研究院,环境与生态安全技术研究所,河南郑州450001 [3]西南大学化学化工学院,重庆市高校应用化学重点实验室,重庆400715

出　　处：《化学研究与应用》2023年第2期295-302,共8页Chemical Research and Application

基　　金：国家自然科学基金青年基金项目(201805208)资助;河南省科技攻关项目(212102310487)资助;中央高校基本科研业务经费(2019TJJBKY032,2020TJJBKY005)资助。

摘　　要：酒精和毒品的共同滥用已经成为国内外社会关注的重点问题之一,共同滥用条件下的体内活性协同增强的相关研究备受关注。本文通过构建体外人肝微粒体代谢模型、尿苷二磷酸葡萄糖醛酸基转移酶(UGT2B7)抑制模型以及大鼠体内代谢模型,并利用气质联用仪对吗啡及其代谢产物进行分析,探索共同滥用条件下乙醇对吗啡活性协同增强的影响。研究结果发现在体外肝微粒体和酶抑制代谢模型中,相对于无乙醇的对照组,实验组中吗啡的代谢速率因受到体系中乙醇的影响而明显减缓,导致原药吗啡的浓度相对增高(1.2~5.6倍,P<0.01)。与此同时,具有更强活性的代谢产物吗啡-6-葡萄糖醛酸苷(M-6-G)在肝微粒体中也显示出相对较高并持续时间更长的浓度水平。此外,在大鼠体内代谢模型中,乙醇的存在使得吗啡在肝脏中的含量长时间维持在相对较高浓度水平(1.1~4.3倍,P<0.05),M-6-G整体代谢也呈现明显的延缓现象,且能够较长时间维持在一定的浓度水平。代谢模型中乙醇的存在导致吗啡和M-6-G在体内较长时间维持在相对较高浓度水平,二者药效的叠加使得吗啡体内的活性协同增强、作用时间延长,吸食者主观感受增强。To explore the effect of different concentrations of ethanol on synergistic enhancement of morphine toxicity under co-abuse conditions.Human liver microsomes in vitro,enzyme inhibition experiment in vitro and in vivo rat model were employed in this work.The results of liver microsomes metabolic model and UGT2B7 enzyme inhibitory activity metabolic model showed that the metabolic rate of morphine in the experimental group was significantly decreased by ethanol when compared with the control group without ethanol,resulting in a relative increase in the concentration of morphine(1.2~5.6 times,P<0.01).The metabolite morphine-6-glucuronoside(M-6-G)with higher biological activity also showed relatively high and longer-lasting concentration levels.The pres-ence of ethanol keeps morphine concentration levels at relatively high levels for a long time in the rat model(1.1~4.3 times,P<0.05).The overall metabolism of M-6-G is also significantly delayed,and it can be maintained at a certain concentration level for a long time.The presence of ethanol in a metabolic model results in the maintenance of morphine and M-6-G at relatively high con-centrations in vivo for an extended period of time.The superposition of the two drug effects enhances the toxicity of morphine in the body and prolongs the action time,resulting in enhanced subjective feelings of the addicts.

关 键 词：乙醇 吗啡 双重滥用 肝微粒体 协同作用 

分 类 号：O656[理学—分析化学]