Metabonomic Profile of Rats with Acute Liver Rejection

Abstract

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.