Key Laboratory for Laboratory Medicine of Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Medical College, Zhejiang University, 79 Qingchun Road, Institute for Cell-Based Drug Development for Zhejiang Province, Hangzhou City 310003, Zhejiang Province, PR China.
Toxicol Lett. 2014 Mar 21;225(3):358-66. doi: 10.1016/j.toxlet.2014.01.008. Epub 2014 Jan 19.
Metabonomics has emerged as an important technology for exploring the underlying mechanisms of diseases and screening for biomarkers. In this investigation, to comprehensively assess metabolite changes in D-galactosamine (GalN)-induced liver injury in Chinese miniature pigs and to increase our understanding of physiological changes in normal and pathological states, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to analyze metabolites and identify biomarkers in serum. Blood samples were collected both from 18 h after GalN treatment group and control group pigs. We performed multivariate analyses on the metabolite profiles to identify potential biomarkers of acute liver injury, which were then confirmed by tandem MS. Based on "variable of importance in the project" (VIP) values and S-plots, four groups of biomarkers were identified--namely conjugated bile acids, lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and fatty acid amides (FAAs)--that were present at significantly different levels in the control and GalN-induced groups. LPCs, PCs, and FAAs showed marked decreases in the GalN-treated group, whereas conjugated bile acids in the treated group showed considerable increases. Taken together, our results suggested that obvious metabolic disturbances occur during acute liver injury, which provided novel insights into the molecular mechanism(s) of D-galactosamine (GalN)-induced liver injury, and will facilitate future research and management of liver injury.
代谢组学已成为探索疾病潜在机制和筛选生物标志物的重要技术。在本研究中，为了全面评估半乳糖胺（GalN）诱导的中国小型猪肝损伤中的代谢物变化，并增加我们对正常和病理状态下生理变化的理解，我们使用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-QTOF-MS）分析血清中的代谢物并鉴定生物标志物。分别采集 GalN 处理组和对照组猪在 GalN 处理后 18 小时的血液样本。我们对代谢物谱进行多元分析，以鉴定急性肝损伤的潜在生物标志物，然后通过串联质谱进行验证。基于“项目中的重要变量”（VIP）值和 S-图，鉴定出了四组生物标志物——即结合胆汁酸、溶血磷脂酰胆碱（LPC）、磷脂酰胆碱（PC）和脂肪酸酰胺（FAA）——在对照组和 GalN 诱导组之间存在明显差异。LPC、PC 和 FAA 在 GalN 处理组中明显减少，而处理组中的结合胆汁酸则明显增加。总之，我们的研究结果表明，急性肝损伤期间会发生明显的代谢紊乱，这为半乳糖胺（GalN）诱导的肝损伤的分子机制提供了新的见解，并将促进未来肝损伤的研究和管理。
