解吸电喷雾电离飞行时间质谱成像分析大鼠脑组织中小分子神经化学物质的分布  

Analysis of Distribution of Neurochemicals in Rat Brain by Desorption Electrospray Ionization Time-of-Flight Mass Spectrometry Imaging

作　　者：黄鑫 王一凯 修洋 郭云龙 越皓 陈长宝 刘淑莹 HUANG Xin;WANG Yi-Kai;XIU Yang;GUO Yun-Long;YUE Hao;CHEN Chang-Bao;LIU Shu-Ying(Jilin Ginseng Academy,Changchun University of Chinese Medicine,Changchun 130117,China;Changchun Center of Mass Spectrometry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China)

机构地区：[1]长春中医药大学吉林省人参科学研究院,长春130117 [2]中国科学院长春应用化学研究所,长春质谱中心,长春130022

出　　处：《分析化学》2022年第10期1533-1541,共9页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(No.81903778);吉林省科技发展计划项目(No.20200201196JC)资助。

摘　　要：采用解吸电喷雾电离飞行时间质谱成像(DESI-TOF-MSI)技术分析了大鼠脑组织中小分子神经化学物质及其代谢产物的分布。制备大鼠全脑水平切面冷冻切片,采用DESI-TOF-MSI质谱扫描成像,考察喷雾溶剂组成及比例对神经化学物质分别在正离子和负离子模式下的检测信号强度的影响。对比正、负离子模式下的高分辨质谱信息及HMDB数据库检索分析,在大鼠脑组织中共检测到25种神经化学物质及其代谢产物,并且在0.1%甲酸-甲醇喷雾溶剂条件下检测到神经化学物质分子离子峰信号强度提升最大。应用HDImaging v1.5软件对数据进行精细成像分析,结果表明,喷雾溶剂中添加0.1%甲酸对成像效果的提升程度与质谱信号强度提升趋势相似,并且本方法具有较高的重复性。其中,γ-氨基丁酸和天冬氨酸主要分布在大脑皮层中,丝氨酸在全脑分布,谷氨酰胺分布于海马区周围,神经化学物质与其前体和主要代谢产物在脑中的空间分布区域相同。本研究结果表明,DESI-TOF-MSI技术可用于大鼠脑组织中小分子神经化学物质分布的分析,为小分子神经化学物质在脑中的空间分布和空间代谢研究提供了快速、有效的可视化分析方法。The distribution of small molecular neurochemicals and their metabolites in rat brain was analyzed by desorption electrospray ionization time-of-flight mass spectrometry imaging(DESI-TOF-MSI)technique.The whole brain frozen horizontal sections of rats were prepared and scanned by DESI-TOF-MSI imaging.The influences of composition and proportion of spray solvents on the signal intensity of neurochemicals under positive and negative ion modes were also investigated.By comparison of high resolution mass spectrometry information in positive and negative ion mode and HMDB database searching,25 kinds of neurochemicals and their metabolites were detected in rat brain.Under the condition of 0.1%formic acid-methanol spray,the molecular ion intensity of neurochemicals was increased mostly.HDImaging v1.5 was used for fine imaging analysis.Addition of 0.1%formic acid to the spray solvent could improve the imaging effect similar to the increasing trend of mass signal intensity.The method presented high repeatability.γ-Aminobutyric acid and aspartic acid were mainly distributed in cerebral cortex.Serine was detected throughout the brain.Glutamine was distributed around the hippocampus.The same spatial distribution of neurochemicals and their precursors and major metabolites in the brain was detected.The DESI-TOF-MSI technique developed here could be used to analyze the distribution of small molecular neurochemicals in rat brain.This work provided a fast and effective visualization method for the study of spatial distribution and metabolism of small molecule neurochemicals in brain.

关 键 词：解吸电喷雾电离飞行时间质谱成像 神经化学物质 脑组织 分布 

分 类 号：O657.63[理学—分析化学] Q503[理学—化学]