基质辅助激光解吸电离-质谱成像技术(MALDI-MSI)及其在脑神经性疾病研究中的应用

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging and its Application in the Study of Brain Neurological Disease

大脑是人体内结构最精细、功能最复杂的高级器官,其化学物质种类众多、功能多样、作用机制复杂。研究证明,脑中枢神经系统疾病的病变脑组织都涉及到一些神经分子的改变。但由于分析检测手段、样品制备、成像技术等原因,对脑神经组织进行成分分析、功能鉴定、空间分布等研究一直是个难点。随着质谱技术的发展和成像软件的发展,一种新分析检测方法,质谱成像技术(Mass Spectrometry Imaging,MSI)应运而生。该技术把高灵敏度的质谱和提供检测物空间信息的成像软件相结合,是一种具有高灵敏、没有特异性标记且可同时监测多种目标分子空间分布和含量变化的成像技术,为绘制脑神经组织中分子的空间分布和含量变化提供了新的选择。其中,基质辅助激光解吸电离-质谱成像技术(Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging,MALDIMSI)在蛋白质、脂质、药物和小分子物质检测上的优势显著,广泛应用于生物组织的成像研究,尤其是脑神经组织。目前,随着一些MSI定量分析方法和校正策略的出现,定量质谱成像技术(q-MSI)越来越成熟,不仅可用于可视化生物组织中各种分子的含量及原位分布信息,还可提供浓度的绝对分析,具有广阔的应用前景。本文旨在简要介绍MALDI-MSI的基本原理、操作流程、样品处理、基质选择与喷涂、数据采集与分析,质谱成像的定性、定量分析方法,并对该技术在常见脑神经疾病(如帕金森病、阿尔茨海默病、多发硬化症、脑损伤和缺血性脑卒中等)中的应用进展进行综述,有助于了解脑中枢神经功能、疾病形成机制和神经药物的代谢机理,有利于发现新的药物靶点以及生物标志物,为研究其治疗策略的潜在机制提供参考,并对未来发展方向进行了展望。

The brain is a high-level organ with the most delicate structure and complex function in the human body,with a large variety of chemicals,diverse functions,and complex mechanisms of action.Studies have shown that changes in some molecules are involved in cerebral neuropathy tissues in the study of central nervous system diseases.However,due to the analysis and detection methods,sample preparation,imaging technology,and other reasons,it has always been difficult to conduct research on the component analysis,functional identification,and spatial distribution of brain nerve tissue.With the development of mass spectrometry technology and the development of imaging software,a new analysis and detection method,Mass Spectrometry Imaging(MSI),has emerged.This technique combines highly sensitive mass spectrometry with imaging software that provides spatial information of detectors,and is an imaging technique with high sensitivity,no specific labeling,and can monitor the spatial distribution and content changes of multiple target molecules simultaneously,providing a new option for mapping the spatial distribution and content changes of molecules in brain neural tissue.Among them,Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI)has significant advantages in the detection of proteins,lipids,drugs,and small molecules,and is widely used in biological It has been widely used in imaging studies of biological tissues,especially brain neural tissue.At present,with the emergence of some MSI quantitative analysis methods and correction strategies,quantitative mass spectrometry imaging technology(q-MSI)is becoming more and more mature.It can not only be used to visualize the content and in-situ distribution information of various molecules in biological tissues,but also provide absolute analysis of concentration.This paper aims to briefly introduce the basic principle,operation process,sample processing,matrix selection,and spraying,data acquisition and analysis,qualitative and quantitative analysis methods of mass spectrometry imaging,and summarize the application progress of MALDI-MSI in common brain diseases such as Parkinson’s disease,Alzheimer’s disease,multiple sclerosis,brain injury and ischemic stroke,which is helpful to understand the function of brain central nervous system The mechanism of disease formation and the metabolism of neuro drugs are conducive to the discovery of new drug targets and biomarkers,provide a reference for the study of the potential mechanism of its treatment strategy,and look forward to the future development direction.