Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Aug 15;879(24):2369-75. doi: 10.1016/j.jchromb.2011.06.018. Epub 2011 Jun 17.
Alcohol abuse is one of the major causes of liver injury and a promoter for hepatocellular carcinoma (HCC). To understand the disease-associated metabolic changes, we investigated and compared the profiles of metabolites in nude mice with alcohol-induced liver injury or bearing a HCC xenograft (HCCX). Alcohol-induced liver injury was achieved by daily administration of grain liquor, and HCC xenografts were generated by subcutaneous inoculation of HepG2 cells in nude mice. Metabolites in serum samples were profiled by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). The acquired data was analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to identify potential disease-specific biomarkers. Results showed that the phosphatidylcholine (PC) levels were significantly higher in both liver injury and HCCX mice compared with the control. Interestingly, lysophosphatidylcholines (LPCs) that contain saturated or monounsaturated fatty acids were reduced in both liver injury and HCCX mice, but polyunsaturated fatty acids LPCs were elevated in liver injury mice only. These data delineated the disease-related metabolic alterations of LPCs in liver injury and HCC, suggesting that the LPC profile in serum may be biomarkers for these two common liver diseases.
酒精滥用是肝损伤的主要原因之一，也是肝细胞癌（HCC）的促进因素。为了了解与疾病相关的代谢变化，我们研究并比较了酒精性肝损伤裸鼠和 HCC 异种移植（HCCX）裸鼠血清中代谢物的特征。通过每天给予白酒来诱导酒精性肝损伤，通过将 HepG2 细胞皮下接种到裸鼠中生成 HCC 异种移植。通过超高效液相色谱-四极杆飞行时间质谱联用仪（UPLC/Q-TOF MS）对血清样本中的代谢物进行分析。通过主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）对获得的数据进行分析，以鉴定潜在的疾病特异性生物标志物。结果表明，与对照组相比，肝损伤和 HCCX 小鼠的磷脂酰胆碱（PC）水平明显升高。有趣的是，肝损伤和 HCCX 小鼠中含饱和或单不饱和脂肪酸的溶血磷脂酰胆碱（LPC）降低，但仅在肝损伤小鼠中多不饱和脂肪酸 LPC 升高。这些数据描绘了 LPC 在肝损伤和 HCC 中的疾病相关代谢变化，表明血清中 LPC 谱可能是这两种常见肝病的生物标志物。
