色谱

色谱 ›› 2015, Vol. 33 ›› Issue (7): 683-690.DOI: 10.3724/SP.J.1123.2015.04007

• 研究论文 • 上一篇    下一篇

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

刘晓燕1, 刘艳秋2, 程孟春1, 肖红斌1,3   

  1. 1. 中国科学院大连化学物理研究所, 中国科学院分离分析化学重点实验室, 辽宁 大连 116023;
    2. 大连医科大学中西医结合学院(研究院), 辽宁 大连 116044;
    3. 北京中医药大学, 北京 100029
  • 收稿日期:2015-04-03 出版日期:2015-07-08 发布日期:2015-07-27
  • 通讯作者: 肖红斌
  • 基金资助:

    国家科技重大专项(2014ZX09304307-001-006).

Application of ultra high performance liquid chromatography- mass spectrometry to metabolomics study of drug-induced hepatotoxicity

LIU Xiaoyan1, LIU Yanqiu2, CHENG Mengchun1, XIAO Hongbin1,3   

  1. 1. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;
    2. College (Institute) of Integrative Medicine, Dalian Medical University, Dalian 116044, China;
    3. Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2015-04-03 Online:2015-07-08 Published:2015-07-27

PDF

226

被引次数

5

摘要：

药物引起的肝损伤是全世界关注的健康问题,药源性肝损伤的早期诊断仍然是临床治疗肝损伤的一大难题。本研究中,首先利用对乙酰氨基酚、四氯化碳、大黄素、雷公藤甲素和马兜铃酸构建不同类型的肝细胞损伤模型,利用超高效液相色谱-质谱联用技术(UPLC-MS)分别得到正常组和损伤组的细胞代谢轮廓谱。然后利用模式识别构建分类模型,筛选肝损伤相关的差异代谢物。结果显示,不同类型肝损伤在肝细胞代谢谱上可以被区分开,最终鉴定出14种差异代谢物。损伤组肝细胞经保肝阳性药联苯双酯干预后,差异代谢物水平均趋向于正常组,在一定程度上验证了差异标志物与肝损伤的相关性。实验结果表明细胞代谢组学是研究药物肝损伤的有效工具之一。

关键词: 超高效液相色谱-质谱, 代谢组学, 肝损伤

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 triptolide (18 nmol/L), separately. Global metabolomics profiling, multivariate analysis and database searching were performed to discover common differential metabolites for live injury. The positive hepatoprotective drug, bifendate, was used to repair triptolide induced hepatocytes injury, and bifendate-induced changes of hepatotoxicity-related metabolites were investigated. In the results, fatty acid oxidation and cellular oxidative stress-related metabolites, including nicotinamide adenine dinucleotide and glutathione were significantly changed between the control and hepatotoxicant-treated groups, and after treatment with bifendate, those perturbed metabolites 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 effective tools to investigate drug-induced hepatotoxicity.

Key words: hepatotoxicity, metabolomics, ultra high performance liquid chromatography-mass spectrometry (UPLC-MS)

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