1H NMR-based metabonomics study on serum of renal interstitial fibrosis rats induced by unilateral ureteral obstruction

Abstract

Renal fibrosis is the common pathway of progressive renal disease with complex pathogenesis. Investigating the metabolic changes in the evaluation process of renal fibrosis may enhance the understanding of its pathogenesis. In this study, ¹H nuclear magnetic resonance (¹H NMR) measurements combined with multivariate statistical techniques were performed to study the metabolic changes in serum samples of renal interstitial fibrosis (RIF) rats, induced by unilateral ureteral obstruction (UUO). Partial least squares-discriminant analysis (PLS-DA) showed satisfactory clustering between UUO and sham operation (SO) rats, suggesting that the metabolic profiles of the RIF groups are markedly different from those of the controls. Alterations in the levels of some metabolites such as valine, isoleucine, lactate, 3-hydroxybutyrate, alanine, acetate, acetoacetate, pyruvate, and glutamate, with time dependence in UUO rats, were observed in PLS-DA loading plots. These changed metabolites represent potential metabolic biomarkers and provide clues that can elucidate the mechanisms underlying the generation and development of RIF. Enhanced metabolic pathways of lipid and ketone body synthesis were predominant in RIF rats. Energy metabolism seemed to be impaired at the early stage of fibrosis but enhanced at a late stage. Our results suggest that ¹H NMR-based metabonomics can provide novel insights into the pathogenesis of RIF.