1H NMR studies on serum metabonomic changes over time in a kidney-Yang deficiency syndrome model

Abstract

The central aim of this study was to investigate metabolite changes in metabolic pathways via metabonomic approaches in rats suffering from Kidney-Yang Deficiency Syndrome (KYDS) induced by hydrocortisone. Metabonomic analysis using ¹H NMR is a well-established approach for the study of metabolic changes in biofluids. In our study, serum samples were obtained at three specific time points during the progression of KYDS, and individual ¹H NMR spectra were acquired and statistically assessed using two multivariate analyses (MVA): principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The profiles on the 15^th, 23^rd, and 30^th day for each sample could be classified, further revealing progression axes from a normal status to KYDS status. Consequently, significant changes in seventeen metabolites, i.e. lactate, valine, alanine, methionine, succinate, glutamine, 3-hydroxybutyrate, creatine, choline, HDL, LDL, VLDL, TMAO, betaine, tyrosine, citrate, and glycerol, were identified. These biochemical changes were found to be directly related to disturbances in energy metabolism, amino acid metabolism, lipid metabolism, choline metabolism, and gut metabolism. We further determined that lactate and the other 16 metabolic markers may be used as specific markers of KYDS over time. Overall, this study demonstrates that this metabonomic method is a valuable tool for studying the pathologic changes of the Chinese medicine syndrome and the underlying mechanisms of KYDS.