超高效液相色谱-四极杆/静电场轨道阱高分辨质谱探究4-HO-MiPT染毒斑马鱼脑部代谢组学变化

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中文摘要：为评价色胺类新精神活性物质 4-羟基-N-甲基-N-异丙基色胺(4-HO-MiPT)对大脑的毒性效应,本实验以斑马鱼为模式生物进行自发活动行为记录分析,采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UHPLC-Q/Orbitrap HRMS)分析斑马鱼大脑长期染毒后的代谢产物,并在转录水平上检测斑马鱼脑部目标基因的变化.结果表明,注射药物 4-HO-MiPT后,斑马鱼运动速度明显减慢,运动范围明显缩小.从斑马鱼大脑检测出 37种差异代谢产物,其中 7种升高,30种降低,并导致 6条代谢通路改变.脑部基因转录水平检测发现,4个神经系统的基因转录水平下降,对大脑细胞产生影响.本实验证明了 4-HO-MiPT对斑马鱼大脑产生毒性效应,对神经系统、免疫功能造成损害并影响体内代谢,对斑马鱼行为产生明显的抑制效果,同时从 4-HO-MiPT造成的内源性影响推测其可能致癌.

外文标题：Study on the Brain Metabolomic Changes of 4-HO-MiPT Infected Zebrafish by UHPLC-Q/Orbitrap HRMS

外文摘要：This study aimed to assess the neurotoxic effects of the novel psychoactive substance 4-hydroxy-N-methyl-N-isopropyltryptamine(4-HO-MiPT)on brain.By employing zebrafish as a model organism,the study applied a multifaceted approach,including the recording and analysis of spontaneous behavioral activities,identification of brain metabolic products via ultra-high performance liquid chromatography coupled with quadrupole-Orbitrap high resolution mass spectrometry(UHPLC-Q/Orbitrap HRMS),and examination of changes in the transcriptional level of target genes.Following the injection of 4-HO-MiPT,zebrafish exhibites a pronounced reduction in movement speed and range,indicating a significant alteration in locomotor activity.The subsequent analysis of brain metabolic products finds 37 differential metabolites,including 7 elevated and 30 reduced ones,alongside notable alterations in 6 metabolic pathways.Moreover,the examination of transcriptional level of key genes in zebrafish brain underscores a discernible decrease in transcriptional level of genes associated with the nervous system,implying a substantial impact on neuronal function and synaptic transmission.The experimental findings substantiate the neurotoxic effects of 4-HO-MiPT on the zebrafish brain,shedding light on its deleterious repercussions on both the nervous and immune systems.Furthermore,the perturbations observed in metabolic processes and behavioral responses emphasize the profound impact of 4-HO-MiPT exposure on fundamental physiological functions.The identification of potential carcinogenicity associated with 4-HO-MiPT further underscores the urgent need for comprehensive risk assessment and regulatory scrutiny.This study represents a crucial step towards unraveling the intricate neurotoxic mechanisms underlying 4-HO-MiPT exposure.The research has far-reaching implications,not only in advancing our understanding of the adverse health effects associated with novel psychoactive substances,but also in guiding the development of targeted interventions and regulatory strategies aiming at safeguarding public health and well-being.Continued exploration into the long-term consequences of 4-HO-MiPT exposure,alongside comprehensive toxicological evaluations,holds promise in mitigating its potential hazards and ensuring the safety of individuals and communities exposed to this emerging threat.

外文关键词：

4-hydroxy-N-methyl-N-isopropyltryptamine(4-HO-MiPT)ultra-high performance liquid chromatography coupled with quadrupole-Orbitrap high resolution mass spectrometry(UHPLC-Q/Orbitrap HRMS)zebrafishbehavioral modelmetabolomics

作者：

陈宇彬、于交远、孟梁、刘猛、赵森

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作者单位：

浙江警察学院,浙江省毒品防控技术研究重点实验室,浙江杭州 310053

呼伦贝尔市公安局刑事侦查支队,内蒙古呼伦贝尔 021001

福建警察学院,福建福州 350007

关键词：

4-羟基-N-甲基-N-异丙基色胺(4-HO-MiPT) 超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UHPLC-Q/Orbitrap HRMS) 斑马鱼行为模型代谢组学

基金：

国家重点研发计划浙江省自然科学基金公安部科技项目

项目编号：

2023YFC3303903-3LGF21B0500022023JSM06

出版年：

2024

DOI：

10.7538/zpxb.2023.0126

质谱学报

北京中科科仪技术发展有限责任公司中国物理学会质谱分会

质谱学报

CSTPCD北大核心EI

影响因子：1.046

ISSN：1004-2997

年,卷(期)：2024.45(5)