摘要
斑马鱼具有体型小、易于饲养、繁殖成本低、繁殖率高等诸多优势,是药物代谢研究的新型模式生物。本文概述斑马鱼代谢模型的构建,介绍斑马鱼模型的基因与人类高度相似性以及其发达的酶系统、较低的基质效应等优点;总结斑马鱼模型在合成大麻素类、芬太尼类、哌嗪类、合成卡西酮类等各类新精神活性物质研究中的应用;综述斑马鱼中体内常见的代谢反应包括Ⅰ相(氧化、N-脱甲基、O-脱乙基化、羟化和N-脱烷基)和Ⅱ相(硫酸化和葡萄糖醛酸化)反应,说明其代谢物种类与真实人体体液样本之间的差异主要和酶的种类有关,指出斑马鱼模型在研究新精神活性物质方面的巨大潜力和进一步研究趋势。
Zebrafish is a novel model organism for drug metabolism research because of its small size,easy feeding,low reproduction cost and high reproduction rate.This paper outlines the construction of zebrafish metabolic model,illustrating the advantages of zebrafish model with high genetic similarity to human,welldeveloped enzyme system,and low substrate effect;and then reviews the application of zebrafish model in the synthesis of various new psychoactive substances such as cannabinoids,fentanyl,piperazines,and synthetic cathinones.The common metabolic reactions in zebrafish,including phase I(oxidation,N-demethylation,Odeethylation,hydroxylation and N-desalkylation)and phase II(sulfation and glucuronidation)reactions,are summarized,and the differences between the metabolites of zebrafish and those of real human body fluid samples are mainly related to the types of enzymes.This paper also points out the great potential and further research trends of zebrafish model in the study of new psychoactive substances.
作者
许琳灏
刘信泽
刘伟
向平
杭太俊
阳硕
严慧
XU Linhao;LIU Xinze;LIU Wei;XIANG Ping;HANG Taijun;YANG Shuo;YAN Hui(Shanghai Key Laboratory of Forensic Medicine,Shanghai Forensic Science Platform,Key Laboratory of Forensic Science,Ministry of Justice,Academy of Forensic Science,Shanghai 200063;School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2022年第5期606-612,共7页
Journal of China Pharmaceutical University
基金
上海市人才发展资助项目(No.2019095)
上海市自然科学基金资助项目(No.19ZR1458800)
上海市法医学重点实验室资助项目(No.21DZ2270800)
上海市司法鉴定专业技术服务平台资助项目(No.19DZ2292700)。
关键词
斑马鱼模型
新精神活性物质
代谢物
应用
zebrafish model
new psychoactive substance
metabolite
application
