RESUMO
Acute pancreatitis (AP) is a progressive systemic inflammatory response with high morbidity and high mortality, which is mainly caused by alcohol, bulimia, gallstones and hyperlipidemia. The early diagnosis of different types of AP and further explore potential pathophysiological mechanism of each type of AP is beneficial for optimized treatment strategies and better patient's care. In this study, a metabolomics approach based on gas chromatography-mass spectrometry (GC-MS), and random forests algorithm was established to distinguish biliary acute pancreatitis (BAP), Hyperlipidemia acute pancreatitis (HLAP), and alcoholic acute pancreatitis (AAP), from healthy controls. The classification accuracies for BAP, HLAP, and AAP patients compared with healthy control, were 0.886, 0.906 and 0.857, respectively, by using 5-fold cross-validation method. And some special metabolites for each type of AP were discovered, such as l-Lactic acid, (R)-3-Hydroxybutyric acid, Phosphoric acid, Glycine, Erythronic acid, l-Phenylalanine, d-Galactose, l-Tyrosine, Arachidonic acid, Glycerol 1-hexadecanoate. Furthermore, associations between these metabolites with the metabolism of amino acids, fatty acids were identified. Our studies have illuminated the biomarkers and physiological mechanism of disease in a clinical setting, which suggested that metabolomics is a valuable tool for identifying the molecular mechanisms that are involved in the etiology of BAP, AAP, HLAP and thus novel therapeutic targets.
Assuntos
Metabolômica/métodos , Pancreatite/diagnóstico , Pancreatite/metabolismo , Doença Aguda , Adulto , Algoritmos , Aminoácidos/análise , Aminoácidos/metabolismo , Doenças Biliares/complicações , Doenças Biliares/diagnóstico , Biomarcadores/análise , Diagnóstico Diferencial , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/diagnóstico , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Pancreatite Alcoólica/complicações , Pancreatite Alcoólica/diagnóstico , Reprodutibilidade dos TestesRESUMO
Alcohol abuse is commonly associated with the development of both acute and chronic pancreatitis. Despite this close association, the fact that only a small percentage of human beings who abuse alcohol develop pancreatitis indicates that alcohol abuse alone is not sufficient to initiate clinical pancreatitis. This contention is further supported by the fact that administration of ethanol to experimental animals does not cause pancreatitis. Because of these findings, it is widely believed that ethanol sensitizes the pancreas to injury and additional factors trigger the development of overt pancreatitis. How ethanol sensitizes the pancreas to pancreatitis is not entirely known. Numerous studies have demonstrated that ethanol and its metabolites have a number of deleterious effects on acinar cells. Important acinar cells properties that are affected by ethanol include: calcium signaling, secretion of zymogens, autophagy, cellular regeneration, the unfolded protein response, and mitochondrial membrane integrity. In addition to the actions of ethanol on acinar cells, it is apparent that ethanol also affects pancreatic stellate cells. Pancreatic stellate cells have a critical role in normal tissue repair and the pathologic fibrotic response. Given that ethanol and its metabolites affect so many pancreatic functions, and that all of these effects occur simultaneously, it is likely that none of these effects is "THE" effect. Instead, it is most likely that the cumulative effect of ethanol on the pancreas predisposes the organ to pancreatitis. The focus of this article is to highlight some of the important mechanisms by which ethanol alters pancreatic functions and may predispose the pancreas to disease.