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正负离子切换扫描质谱成像分析方法及其整体动物体内代谢应用研究
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作者单位
黄建鹏,张锦,刘丹,高杉杉,张瑞萍,贺玖明 中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室 
基金项目:国家自然科学基金面上项目(81974500、81773678)
中文摘要:基于质谱成像(MSI)技术的空间分辨代谢组学方法已经成为生物组织学、肿瘤分子病理诊断和新药药效毒理研究的有力工具。该研究采用敞开式空气动力辅助解吸电喷雾离子化(AFADESI)技术,开发了一种正负离子切换扫描的质谱成像方法。该方法在离子化过程中无需施加高电压,既提高了敞开式离子化质谱成像的操作安全性,还可将生物组织切片,尤其是较大面积的整体动物组织切片中的各类不同性质的内源性代谢物进行高效率解吸和离子化,同时获得多胺、氨基酸、磷脂(正离子模式易电离)和核苷、磷脂酰甘油(负离子模式易电离)等内源性代谢物的空间分布特征。通过正负离子化的同时扫描和质谱成像分析,节省了数据采集的时间和样本切片的数量,扩展了代谢物的覆盖范围,使得一次实验可以成像检出更多种类的代谢物。因此,该方法在整体动物各组织器官的空间分辨代谢组学研究中具有优势,有望从整体动物体内代谢水平深刻理解与生理、病理和药理相关的分子空间分布特征及分子机制。
中文关键词:质谱成像(MSI)  空间分辨代谢组学  空气动力辅助解吸电喷雾离子化(AFADESI)  整体动物组织
 
A Positive/Negative Ion Mode-switched Mass Spectrometry Imaging Method and Its Application in Metabolomics Analysis of Whole-body Animals
Abstract:Spatially resolved metabolomics methods based on mass spectrometry imaging(MSI) technology have become a powerful tool for biological histology,molecular pathological diagnosis of tumor,and new drug efficacy and toxicology research.In this study,air flow assisted desorption electrospray ionization(AFADESI) with positive/negative mode switched scan was developed for MS imaging.With no need to apply high voltage during the ionization process,this method could not only improve the operating safety of ambient ionization,but also efficiently desorb and ionize various endogenous metabolites from biological tissue slices,especially large area whole body animal tissue slices.Furthermore,it could obtain the spatial distribution characteristics of those metabolites including polyamines,amino acids,phospholipids(easy to ionize in positive ion mode),nucleosides and phosphatidylglycerol(easy to ionize in negative ion mode).Through the simultaneous MSI analysis in positive or negative ion mode,the data collection time and the number of sample slices were saved,and the coverage of metabolites was expanded,while more types of metabolites could be detected in single experiment.Therefore,this method has the advantages in the spatially resolved metabolomics research on various tissues and organs of whole body animals,and it is expected to deeply understand the molecular spatial distribution characteristics and molecular mechanisms related to physiology,pathology and pharmacology at the metabolic level.
Key Words:mass spectrometry imaging(MSI)  spatially resolved metabolomics  air flow assisted desorption electrospray ionization(AFADESI)  whole body animal
引用本文:黄建鹏,张锦,刘丹,高杉杉,张瑞萍,贺玖明.正负离子切换扫描质谱成像分析方法及其整体动物体内代谢应用研究[J].分析测试学报,2021,40(2):256-262.
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