Metabonomic Investigation on Plasma Samples of Liver Transplanted Rats

Abstract

In recent years, more sensitive and less invasive methods for detecting organ transplantation rejection have been receiving increasing interest. Metabonomics is a recent development in the transplantation field. In this paper, a metabonomic investigation on plasma samples of liver transplanted rats was presented. Samples from control, syngeneic, and allogeneic transplanted groups were analyzed using GC-MS after derivatization. Thirty-six metabolites in the acquired GC-MS data, including amino acids, organic acids, carbohydrates, and some other metabolites were identified and matched by NIST spectral library. The scores plot of principal component analysis (PCA) showed that the three groups were unambiguously apart from each other; the syngeneic liver transplanted group and the control group were adjacent, indicating a high similarity between the two groups; the allogeneic liver transplanted group, however, was apparently separate from the other two groups, demonstrating the significant differences of metabonomic profiles among the groups with or without immunologic reaction. Among the identified thirty-six metabolites, galactose, D-glucose, L-deoxyglucose, gulose, cholesterol, urea, and L-aspartic acid were found to be the significantly changed metabolites according to PCA loadings plot. In the allogeneic liver transplanted group, levels of cholesterol, urea, and L-aspartic acid increased but galactose, D-glucose, L-deoxyglucose, and gulose levels declined compared to those in the control and the syngeneic liver transplanted groups.

Keywords:

• GC-MS
• Liver transplant
• Metabonomics
• Principal component analysis
• Rejection

Acknowledgments

This study was financially supported by Open Project of Shanghai Key Laboratory for Pharmaceutical Metabolites Research (No. 2008SHDX1001), National Natural Science Foundation of China (No. 30901981), and Shanghai Key Laboratory for Pharmaceutical Metabolites Research founded by Science & Technology Department of Shanghai, China. (Grant No. 04DZ19216).

Notes

^a The relative peak areas of the identified 36 metabolites in the control, syngeneic, and allogeneic transplanted groups. Values are expressed with their peak areas normalized to internal standard and represented as mean ± S.D. Significant differences between the syngeneic transplanted group (n = 5) vs. control group (n = 5) and between the allogeneic transplanted group (n = 5) vs. control group (n = 5) were both based on the two-detailed Student's t test (*p < 0.05, **p < 0.01).