Department of Emergency, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China.
Clinical Research Center for Emergency and Critical Care in Hunan Province, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
Front Endocrinol (Lausanne). 2023 Feb 16;14:1060470. doi: 10.3389/fendo.2023.1060470. eCollection 2023.
Sepsis is a life-threatening condition secondary to infection that evolves into a dysregulated host response and is associated with acute organ dysfunction. Sepsis-induced cardiac dysfunction is one of the most complex organ failures to characterize. This study performed comprehensive metabolomic profiling that distinguished between septic patients with and without cardiac dysfunction.
Plasma samples collected from 80 septic patients were analysed by untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics. Principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA), and orthogonal partial least square discriminant analysis (OPLS-DA) were applied to analyse the metabolic model between septic patients with and without cardiac dysfunction. The screening criteria for potential candidate metabolites were as follows: variable importance in the projection (VIP) >1, < 0.05, and fold change (FC) > 1.5 or < 0.7. Pathway enrichment analysis further revealed associated metabolic pathways. In addition, we constructed a subgroup metabolic analysis between the survivors and non-survivors according to 28-day mortality in the cardiac dysfunction group.
Two metabolite markers, kynurenic acid and gluconolactone, could distinguish the cardiac dysfunction group from the normal cardiac function group. Two metabolites, kynurenic acid and galactitol, could distinguish survivors and non-survivors in the subgroup analysis. Kynurenic acid is a common differential metabolite that could be used as a candidate for both diagnosis and prognosis for septic patients with cardiac dysfunction. The main associated pathways were amino acid metabolism, glucose metabolism and bile acid metabolism.
Metabolomic technology could be a promising approach for identifying diagnostic and prognostic biomarkers of sepsis-induced cardiac dysfunction.
脓毒症是一种由感染引起的危及生命的疾病，其特征为宿主反应失调，并伴有急性器官功能障碍。脓毒症引起的心脏功能障碍是最复杂的器官衰竭之一。本研究进行了全面的代谢组学分析，以区分有和无心脏功能障碍的脓毒症患者。
对 80 例脓毒症患者的血浆样本进行非靶向液相色谱-质谱（LC-MS）代谢组学分析。采用主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和正交偏最小二乘判别分析（OPLS-DA）对有和无心脏功能障碍的脓毒症患者的代谢模型进行分析。潜在候选代谢物的筛选标准为：变量重要性投影（VIP）>1、<0.05 和倍数变化（FC）>1.5 或<0.7。通路富集分析进一步揭示了相关代谢途径。此外，我们根据心脏功能障碍组 28 天死亡率对幸存者和非幸存者进行了亚组代谢分析。
两种代谢物标志物，犬尿酸和葡萄糖酸内酯，可区分心脏功能障碍组和正常心脏功能组。两种代谢物，犬尿酸和半乳糖醇，可区分亚组分析中的幸存者和非幸存者。犬尿酸是一种常见的差异代谢物，可作为诊断和预测脓毒症伴心脏功能障碍患者的候选物。主要相关途径为氨基酸代谢、葡萄糖代谢和胆汁酸代谢。
代谢组学技术可能是识别脓毒症引起的心脏功能障碍的诊断和预后生物标志物的有前途的方法。
