GC-MS - based postoperative cognitive disorders of aging rats metabolomics research
|School||Central South University|
|Keywords||Metabolomics Postoperative cognitive dysfunction (POCD) Gas chromatography mass spectrometry (GC-MS) Metabolic profiling Chemomatrics Biomarker|
Postoperative cognitive dysfunction (POCD) is a subtle cognitive dysfunction especially memory for weeks or months after surgery. The underlying pathophysiological mechanisms of POCD are still unclear. The aim of this study was to exploringly study the potential mechanisms of POCD by identifying the differences of metabolic profiles among health control, POCD and no-POCD rats after isoflurane anesthesia, and subsequently discovering POCD potential biomarkers from serum and hippocampus tissue metabolic patterns. Firstly, a metabolic fingerprinting approach of GC-MS combined with two chemometric resolution methods, heuristic evolving latent projections (HELP) and selective ion analysis (SIA), were applied to effectively handle overlapping peaks of GC-MS total ion chromatograms of trimethylsilylated cerebrospinal fluid, serum and hippocampus tissue samples. The metabolic substances in these samples were successfully identified and quantified. Then, the key metabolites screening methods including subwindow permutation analysis (SPA) and competitive adaptive reweighted sampling (CARS) were employed to seek the potential biomarkers of POCD. As a result, pyroglutamic acid, hexadecanoic acid, myo-inositol and cholesterol in serum, myo-inositol, D-galactose,1-monostearin, aspartic acid, pyroglutamic acid, phosphate and unknown compound A in hippocampus tissue were discovered as potential biomarkers of POCD. The metabolic pattern models including principal components analysis (PCA), partial least squares-linear discriminant analysis (PLS-LDA) and the bivariate or trivariate plots for samples based on theses potential biomarkers subsequently revealed the divergences between POCD and no-POCD rats after isoflurane anesthesia. We conclude that the metabolic profiles of hippocampus tissue and serum of POCD were different from no-POCD and health control rats, respectively, and the selected serum and hippocampus metabolites could probably be applied for assisting clinical diagnosis and pathogenesis research for POCD.