Exploring metabolic biomarkers and regulation pathways of acute pancreatitis using ultra-performance liquid chromatography combined with a mass spectrometry-based metabolomics strategy

摘要

Acute pancreatitis (AP), as a common kind of pancreas-based inflammatory disease, is accompanied by a serious and abnormal metabolism. However, the specific metabolic process of AP is still unclear. Novel and effective drugs against acute pancreatitis are urgently required. To explore the metabolic biomarkers and regulation pathways of acute pancreatitis, ultra-performance liquid chromatography (UPLC) combined with a mass spectrometry (MS)-based metabolomics strategy was used. Sixteen male adult Sprague-Dawley rats were divided into two groups: a sham operation group (SO) and an AP model group. The AP animal model was induced via the retrograde ductal infusion of 3.5% sodium taurocholate, and rats in the SO group were infused with 0.9% saline. After serum sample collection and sacrifice, a metabolomics strategy based on UPLC-MS was used to detect serum metabolites and metabolic pathways by comparing the SO and AP model groups through full-scan analysis. A total of 19 metabolites were detected in the serum for highlighting the differences between the two groups: l-arabitol, citric acid, isocitric acid, l-phenylalanine, l-tyrosine, dihydroxyacetone, l-valine, succinic acid, 3-hydroxybutyric acid, uric acid, acetylglycine, palmitic amide, homocysteine, d-glutamine, l-arginine, arachidonic acid, N-acetylserotonin, (R)-3-hydroxy-hexadecanoic acid, and d-mannose. Six crucial metabolic pathways, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism and the citrate cycle, were involved; these have potential to become novel targets for the treatment of AP. The ingenuity pathway analysis (IPA) platform is used to gain insights into the metabolic targets in the system, referring to development disorders, cell-to-cell signaling and interactions, cellular assembly and organization, cell compromise, cell growth and proliferation, carbohydrate metabolism and others. It is suggested that UPLC-MS-based metabolomics is capable of accurately depicting the pathological mechanisms of acute pancreatitis, which can drive new drug development.