Chen Ermei, Lu Juan, Chen Deying, Zhu Danhua, Wang Yini, Zhang Yimin, Zhou Ning, Wang Jie, Li Jianzhou, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Biomed Pharmacother. 2017 Sep;93:480-489. doi: 10.1016/j.biopha.2017.06.049. Epub 2017 Jun 30.
Metabolomics facilitates investigation of the mechanisms of disease and screening for biomarkers. Here, a gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach was employed to identify plasma biomarkers of acute liver failure (ALF) in pigs. Blood was collected from pigs at 12h intervals during ALF. Hepatic injury was quantified by determining liver function and histopathology. Based on a multivariate data matrix and pattern recognition, two upregulated metabolites, namely, amino acids and conjugated bile acids, and two downregulated metabolites, lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs), were identified. All of these metabolites showed a strong relationship with the extent of liver injury. Amino acids were biomarkers of the severity of liver impairment, conjugated bile acids were predictive of early stage liver damage, and LPCs and PCs were related to the prognosis of liver injury. In conclusion, our results demonstrated the occurrence of marked metabolic disturbances during ALF and that integrated metabolomics analysis facilitates identification of biomarkers of disease.
代谢组学有助于疾病机制的研究和生物标志物的筛选。在此，采用基于气相色谱-质谱联用（GC-MS）和超高效液相色谱-质谱联用（UPLC-MS）的代谢组学方法来鉴定猪急性肝衰竭（ALF）的血浆生物标志物。在ALF期间，每隔12小时从猪身上采集血液。通过测定肝功能和组织病理学对肝损伤进行量化。基于多变量数据矩阵和模式识别，鉴定出两种上调的代谢物，即氨基酸和结合胆汁酸，以及两种下调的代谢物，溶血磷脂酰胆碱（LPC）和磷脂酰胆碱（PC）。所有这些代谢物都与肝损伤程度密切相关。氨基酸是肝功能损害严重程度的生物标志物，结合胆汁酸可预测早期肝损伤，而LPC和PC与肝损伤的预后有关。总之，我们的结果表明ALF期间发生了明显的代谢紊乱，并且综合代谢组学分析有助于鉴定疾病的生物标志物。
