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基于液质联用技术的高脂血症金黄地鼠肝脏非靶标代谢组学研究
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孙明谦, 尹春园,苗 兰,张 颖,刘建勋,杨会珍,林 力 中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室北京 100091 
基金项目:国家自然科学基金(81872992,81673587,81803770)
中文摘要:采用液相色谱-飞行时间质谱联用技术(LC-TOF MS)对高脂血症金黄地鼠的肝匀浆液进行代谢谱 分析,并利用模式识别挖掘潜在生物标志物以探索发病机制。采用反相色谱(RPLC)和亲水作用色谱(HILIC) 两种模式分离肝匀浆液中的内源性代谢产物。采用偏最小二乘法判别分析(PLS-DA)进行数据分析,结合标 准品与数据库比对、二级质谱裂解规律对内源性成分进行定性分析。结果显示,模型组和对照组在RPLC和 HILIC两种分离模式下均有良好的区分。与对照组相比,在高脂血症组的金黄地鼠肝脏中鉴定出16种差异代 谢物,其涉及的主要代谢途径为嘌呤代谢、磷脂酰胆碱代谢、鞘脂代谢和赖氨酸代谢等。这些异常的内源性 成分及其生物代谢途径可为了解高脂血症金黄地鼠肝脏发病机制提供依据。
中文关键词:高脂血症  代谢组学  生物标志物  金黄地鼠  液相色谱-飞行时间质谱联用
 
Liver Untargeted Metabolomics of Hyperlip? idemic Hamsters Based on Liquid Chroma? tography-Time-of-flight Mass Spectrometry
Abstract:In this study,metabolic profiles of liver homogenate from hyperlipidemic hamsters were ana? lyzed by liquid chromatography coupled to time-of-flight mass spectrometry,and the potential biomark? ers were explored by pattern recognition method to investigate the pathogenesis. Both reversed-phase (RPLC)chromatography and hydrophilic interaction chromatography(HILIC)were used to separate the endogenous metabolites in liver homogenates. Partial least squares discriminant analysis(PLS-DA) was used to analyze the data,and the qualitative analysis of the endogenous components was carried out by comparing the standards,the database or fragmentation analysis. Good separations were observed be? tween the model and normal groups in both HILIC and RPLC separating modes by PLS-DA. Com? pared with the normal group,16 potential biomarkers in liver of hyperlipidemic group were identified. The major disturbed metabolic pathways were purine metabolism,phosphatidylcholine metabolism, sphingolipids metabolism and lysine metabolism. Results showed that the abnormal biomarkers and pathways may provide evidences to understand the metabolic mechanism of liver in hyperlipidemic ham? sters.
Key Words:hyperlipidemia  metabolomics  biomarkers  hamsters  liquid chromatography-timeof-flight mass spectrometry
引用本文:孙明谦, 尹春园,苗 兰,张 颖,刘建勋,杨会珍,林 力.基于液质联用技术的高脂血症金黄地鼠肝脏非靶标代谢组学研究[J].分析测试学报,2021,40(8):1129-1135.
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