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  

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

作　　者：陈宇彬 于交远 孟梁 刘猛[1] 赵森[1] CHEN Yu-bin;YU Jiao-yuan;MENG Liang;LIU Meng;ZHAO Sen(Key Laboratory of Drug Prevention and Control Technology of Zhejiang Province,Zhejiang Police College,Hangzhou 310053,China;Criminal Investigation Detachment of Hulunbuir Public Security Bureau,Hulunbuir 021001,China;Fujian Police College,Fuzhou 350007,China)

机构地区：[1]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 [2]呼伦贝尔市公安局刑事侦查支队,内蒙古呼伦贝尔021001 [3]福建警察学院,福建福州350007

出　　处：《质谱学报》2024年第5期699-711,共13页Journal of Chinese Mass Spectrometry Society

基　　金：国家重点研发计划(2023YFC3303903-3);浙江省自然科学基金(LGF21B050002);公安部科技项目(2023JSM06)。

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(UHPLCQ/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。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 r

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 

分 类 号：O657.63[理学—分析化学]