基于气相气谱-质谱的代谢组学方法研究四氯化碳致小鼠急性肝损伤  

Gas Chromatography-Mass Spectrometry Based on Metabonomic Study of Carbon Tetrachloride-Induced Acute Liver Injury in Mice

作　　者：黄欣[1] 龚益飞[1] 虞科 程翼宇[1] 

机构地区：[1]浙江大学药物信息学研究所,杭州310058

出　　处：《分析化学》2007年第12期1736-1740,共5页Chinese Journal of Analytical Chemistry

基　　金：国家重点基础研究发展计划(No.2005CB523402);浙江省科技计划重大科技攻关项目(No.2005C13026)资助项目

摘　　要：建立了一种基于气相色谱-质谱(GC-MS)技术的代谢组学分析方法。以CCl4致小鼠肝损伤模型为研究对象,检测了染毒小鼠肝组织和血浆中内源性代谢物随时间的变化情况,并运用主成分分析方法对这一变化过程进行模式识别。研究发现,随着染毒时间的推移,小鼠的整体代谢物谱存在着一定的变化规律。肝组织中苹果酸和部分游离脂肪酸含量升高;血浆中柠檬酸和部分氨基酸含量有所上升。这些代谢物的变化都与肝损程度密切相关,且变化趋势与肝组织病理检查结果一致。研究结果表明:GC-MS技术在代谢物谱的获取和代谢物鉴定方面具有优势,可作为核磁共振(NMR)技术的补充工具用于代谢组学研究。A GC-MS based on methodology was developed to investigate the differences of the metabolite profiles in mice liver tissue and plasma after carbon tetrachloride treatment. NIST mass spectral database was used for the rapid identification of endogenous metabolites, and principal component analysis was introduced for the pattern recognition of mice metabonome. The pattern recognition result presented clear changing tendencies of metabolite profiles at various time postdose, both in liver tissue and plasma. The elevated level of malate and several fatty acids in liver tissue, as well as the increased concentrations of some amino acids and citrate in plasma, could be considered as the response metabolites of CCl4 induced liver injure. Changing tendencies of the metabolite profiles and responsor metabolites were conformed to the histopathological assessment of the liver tissue. The results suggested that GC-MS based on methodology could provide some advantages in metabolite profiles and identification, and therefore could be employed as a potential powerful approach in metabonomic research as a complement of NMR.

关 键 词：气相色谱-质谱 代谢组学 四氯化碳 急性肝损伤 主成分分析法 

分 类 号：R575[医药卫生—消化系统]