法医学杂志

法医学杂志 ›› 2021, Vol. 37 ›› Issue (2): 166-174.DOI: 10.12116/j.issn.1004-5619.2020.401006

• 论著 • 上一篇    下一篇

丁卡因急性中毒致死小鼠血清和组织的代谢组学变化

刘文乔1，2， 白锐1， 马春玲1， 于峰1， 谢冰1， 董玫1， 哈婧2， 文迪1   

  1. 1. 河北医科大学法医学院 河北省法医学重点实验室 河北省法医分子鉴定协同创新中心 河北医科大学法医鉴定中心，河北 石家庄 050017； 2. 河北科技大学化学与制药工程学院，河北 石家庄 050018
  • 收稿日期:2020-10-14 发布日期:2021-04-25 出版日期:2021-04-28
  • 通讯作者: 文迪，男，副主任法医师，教授，主要从事法医毒物学研究；E-mail：wendi01125@126.com 哈婧，女，回族，教授，主要从事药物分析研究；E-mail：hajing02@163.com
  • 作者简介:刘文乔（1990—），女，硕士，主要从事药物分析研究；E-mail：862307735@qq.com
  • 基金资助:
    国家重点研发计划资助项目（2018YFC0807204）

Metabolomics Changes of Serum and Tissues in Mice Died of Acute Tetracaine Poisoning

LIU Wen-qiao1,2, BAI Rui1, MA Chun-ling1, YU Feng1, XIE Bing1, DONG Mei1, HA Jing2, WEN Di1   

  1. 1. Forensic Identification Center of Hebei Medical University, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China; 2. School of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China
  • Received:2020-10-14 Online:2021-04-25 Published:2021-04-28

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摘要： 目的 采用代谢组学方法研究丁卡因急性中毒致死小鼠血清和组织（肾、肝和心脏）中的代谢物变化，寻找潜在的生物标志物及其相关代谢通路，为丁卡因急性中毒的死亡原因鉴定及毒理机制研究提供新思路。 方法 40只ICR小鼠被随机分为对照组和丁卡因急性中毒致死组，以腹腔注射丁卡因建立急性中毒致死模型，运用超高效液相色谱-静电场轨道阱高分辨质谱联用（ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry，UPLC-Orbitrap HRMS）获取小鼠血清和组织的代谢轮廓。利用多元变量统计主成分分析和正交偏最小二乘-判别分析，并结合t检验和差异倍数分析找出与丁卡因急性中毒致死相关的差异代谢物。 结果 与对照组相比，丁卡因急性中毒致死组小鼠血清和组织的代谢轮廓表现出明显的区分。血清中鉴定出11种差异代谢物，包括黄嘌呤、精胺、3-羟基丁胺等；肝组织中鉴定出25种差异代谢物，包括腺苷酸、腺苷、柠檬酸等；心脏中鉴定出12种差异代谢物，包括次黄嘌呤、鸟嘌呤、鸟苷酸等；肾组织中鉴定出4种差异代谢物，包括牛磺鹅去氧胆酸、11，12-环氧二十碳三烯酸、二甲基乙醇胺和吲哚。丁卡因急性中毒主要影响了嘌呤代谢，三羧酸循环，丙氨酸、天冬氨酸和谷氨酸代谢。 结论 丁卡因急性中毒致死小鼠血清和组织中的差异代谢物有望成为该死因的候选生物标志物，该结果可为丁卡因急性中毒的作用机制和死亡原因鉴定提供研究基础。

关键词: 法医病理学, 法医毒理学, 代谢组学, 中毒, 丁卡因, 超高效液相色谱法, 轨道阱, 高分辨质谱法, 小鼠

Abstract: Objective To study the changes of metabolites in serum and tissues （kidney, liver and heart） of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Orbitrap HRMS）. Multivariate statistical principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.

Key words: forensic pathology, forensic toxicology, metabolomics, poisoning, tetracaine, ultra-high performance liquid chromatography （UPLC）, orbitrap, high resolution mass spectrometry （HRMS）, mice

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