本研究旨在揭示与严重急性胰腺炎（SAP）表型相关的代谢异常。采用基于液相色谱-质谱联用技术（LC-MS/MS）的靶向代谢组学分析了106例急性胰腺炎（AP）患者（34例轻型、38例中型和34例重型）在腹痛发作后48小时内入院的血浆样本，以及41名健康对照者的样本。在入院后的第1、3和7天进行了时间性代谢谱分析。采用随机森林（RF）算法确定SAP组与非SAP组代谢物差异。采用质谱成像（MSI）和免疫组化技术分析胰腺组织的代谢物和代谢酶变化，分别在坏死和癌旁组织中进行。同时，应用L-鸟氨酸诱导的AP模型，通过血清和胰腺组织的代谢变化来发现代谢共性。RF筛选出的22种显著差异代谢物用于建立一个准确的SAP与非SAP预测模型（AUC = 0.955）。通过MSI在胰腺病变中发现了其中6种标记物的显著改变，并鉴定了减少的与鸟氨酸相关的代谢物。进一步发现了异常表达的精氨酸酶2和鸟氨酸转甲酰酶。结合SAP动物模型中的时间性代谢谱分析，发现在炎症后期存在鸟氨酸降解产物的减少，但鸟氨酸相关的代谢酶在炎症过程中被激活。AP患者的血浆代谢组学具有独特性，有望用于早期SAP诊断。AP的恶化与激活的鸟氨酸代谢通路以及局部病灶中鸟氨酸降解产物不足有关。版权所有 © 2023。由Elsevier Inc.出版。

To reveal dysregulated metabolism hallmark that was associated with a severe acute pancreatitis (SAP) phenotype.In this study, LC-MS/MS-based targeted metabolomics was used to analyze plasma samples from 106 acute pancreatitis (AP) patients (34 mild, 38 moderate, and 34 severe) admitted within 48 h from abdominal pain onset and 41 healthy controls. Temporal metabolic profiling was performed on days 1, 3 and 7 after admission. A random forest (RF) was performed to significantly determine metabolite differences between SAP and non-SAP (NSAP) groups. Mass spectrometry imaging (MSI) and immunohistochemistry were conducted for the examination of pancreatic metabolite and metabolic enzyme alterations, respectively, on necrosis and paracancerous tissues. Simultaneously determination of serum and pancreatic tissue metabolic alterations using an L-ornithine-induced AP model to discover metabolic commonalities.Twenty-two significant differential metabolites screened by RF were selected to build an accurate model for prediction of SAP from NSAP (AUC = 0.955). Six of 22 markers were found by MSI with significant alterations in pancreatic lesion, reduced ornithine related metabolites were also identified. The abnormally expressed arginase2 and ornithine transcarboxylase were further discovered. And in combination with time-course metabolic profiling in the SAP animal models, the decreased ornithine catabolites were found at a late stage of inflammation, but ornithine-associated metabolic enzymes were activated during the inflammatory process.The plasma metabolome of AP patients is distinctive, which shows promise for early SAP diagnosis. AP aggravation is linked to the activated ornithine metabolic pathway and its inadequate levels of catabolites in in-situ lesion.Copyright © 2023. Published by Elsevier Inc.