Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
OMICS. 2009 Apr;13(2):81-91. doi: 10.1089/omi.2008.0061.
Reliable parameters assessing graft function are essential for the prediction of graft outcome after liver transplantation. Many studies have focused on genomics, transcriptomics, and proteomics using classical methods such as polymerase chain reaction (PCR), Western blotting, etc. Metabonomics is a new area and perspective in the transplantation arena. Little research results regarding metabolism have been achieved; however, serum metabolite profiles from early acute liver rejection models are less well understood. A model of nonarteralized orthotopic liver transplantation (OLT) using Lewis to Brown Norway (BN) rats was preformed. We investigated the variation of serum metabolites by gas chromatography-mass spectrometry (GC-MS) and correlated this change to morphological changes of liver allografts at time points including days 1, 3, 7, and 10 posttransplantation. A significant decrease in serum glucose as well as increase in serum hexadecanoic acid, octadecanoic acid, cholesterol, proline, and threonine have been observed in the serum following transplantation. The total trend in PCA illustrated that serum metabonomic profiles are correlated with the pathological changes seen following liver transplantation. The results of this study suggest that changes in metabonomic profiles reflected in the graft injury are correlated with histological changes instead of classical liver function using traditional biochemical examination. PCA provides support to the investigation of early acute rejection and could become a useful clinical standard in diagnosing the end states of patient. Metabonomics is an efficient technique for detecting graft injury in the early phases of acute rejection.
可靠的评估移植物功能的参数对于预测肝移植后移植物的结果至关重要。许多研究都集中在使用聚合酶链反应(PCR)、Western blot 等经典方法的基因组学、转录组学和蛋白质组学上。代谢组学是移植领域的一个新领域和新视角。关于代谢的研究结果很少,但对于早期急性肝排斥模型的血清代谢物谱了解较少。使用 Lewis 到 Brown Norway(BN)大鼠进行了非动脉化原位肝移植(OLT)模型。我们通过气相色谱-质谱联用(GC-MS)研究了血清代谢物的变化,并将这种变化与移植后第 1、3、7 和 10 天肝移植物的形态变化相关联。移植后,血清中的葡萄糖显著下降,而十六烷酸、十八烷酸、胆固醇、脯氨酸和苏氨酸的血清水平升高。PCA 的总趋势表明,血清代谢组学图谱与肝移植后的病理变化相关。这项研究的结果表明,移植物损伤中反映的代谢组学变化与组织学变化相关,而不是传统生化检查中的经典肝功能。PCA 为研究早期急性排斥反应提供了支持,并可能成为诊断患者终末期的有用临床标准。代谢组学是检测急性排斥反应早期移植物损伤的有效技术。