色谱Issue(7)：683-690,8.DOI:10.3724/SP.J.1123.2015.04007
超高效液相色谱-质谱联用技术在药物肝损伤代谢组学研究中的应用
Application of ultra high performance liquid chromatography-mass spectrometry to metabolomics study of drug-induced hepatotoxicity
摘要
Abstract
Drug-induced hepatotoxicity is a worldwide health issue. And diagnosing the injury in the early stage is still a challenge in clinic. In this study,pattern recognition analysis of the ultra high performance liquid chromatography-mass spectrometry( UPLC-MS)of hepatocytes HL7702 was performed to develop differential metabolites related to hepatotoxicity induced by hepatotoxicants,including carbon tetrachloride(CCl4),acetaminophen(APAP),emodin, aristolochic acid( AA)and triptolide. Hepatocytes injuries were induced by 48 h of treatment with CCl4(4 mmol/L),APAP(6. 5 mmol/L),emodin(14 μmol/L),AA(35 μmol/L)and trip-tolide(18 nmol/L),separately. Global metabolomics profiling,multivariate analysis and data-base searching were performed to discover common differential metabolites for live injury. The positive hepatoprotective drug,bifendate,was used to repair triptolide induced hepatocytes in-jury,and bifendate-induced changes of hepatotoxicity-related metabolites were investigated. In the results,fatty acid oxidation and cellular oxidative stress-related metabolites,including nico-tinamide adenine dinucleotide and glutathione were significantly changed between the control and hepatotoxicant-treated groups,and after treatment with bifendate,those perturbed metab-olites all partly returned to normal level. In conclusion,we discovered potential hepatotoxicity-related metabolites that could be used to evaluate hepatotoxicity induced by chemicals,drugs and traditional Chinese medicines. This study also proved that metabolomics is one of the effec-tive tools to investigate drug-induced hepatotoxicity.关键词
超高效液相色谱-质谱/代谢组学/肝损伤Key words
ultra high performance liquid chromatography-mass spectrometry ( UPLC-MS )/metabolomics/hepatotoxicity分类
化学化工引用本文复制引用
刘晓燕,刘艳秋,程孟春,肖红斌..超高效液相色谱-质谱联用技术在药物肝损伤代谢组学研究中的应用[J].色谱,2015,(7):683-690,8.基金项目
国家科技重大专项（2014ZX09304307-001-006）． （）
