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急性心肌炎患者尿液生物标志物的高通量非靶向代谢组学分析:一项横断面研究。

High-throughput untargeted metabolomic profiling of urinary biomarkers in acute myocarditis patients: a cross-sectional study.

作者信息

Zhao Cui-Mei, Long Xiu-Zhen, Wang Ke-Yi, Tian Shao-Xin, Li Ying-Ran, Zhang Wen-Yuan

机构信息

Department of Pharmacy, Zhongshan City People's Hospital, Zhongshan, 528400, China.

School of Pharmaceutical Sciences, Zunyi Medical University, Zunyi, 563000, China.

出版信息

Sci Rep. 2025 Mar 18;15(1):9254. doi: 10.1038/s41598-025-93655-5.

DOI:10.1038/s41598-025-93655-5
PMID:40102476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11920081/
Abstract

Acute myocarditis, characterized by inflammatory myocardial injury, significantly risks heart failure and sudden death. Despite its severity, specific biomarkers are lacking. This study applied metabolomic analysis to urine samples from 21 acute myocarditis patients and 21 controls using UPLC-MS/MS, revealing 728 increased and 820 decreased metabolites in patients. The affected pathways were predominantly related to the amino acid metabolism, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and others. We have validated 19 metabolites with an area under the receiver operating characteristic curve (AUC-ROC) greater than 0.7 and a high level of identification confidence. Potential biomarkers upregulated in acute myocarditis patients included phytosphingosine, N-acetylneuraminic acid, indolelactic acid, L-glutamic acid, 4-pyridoxic acid, N1-methyl-2-pyridone-5-carboxamide, palmitic acid, hydroxyphenyllactic acid, riboflavin, nicotinic acid, choline, N-formylkynurenine, guanine, and hypoxanthine. Conversely, sebacic acid, 4-vinylphenol sulfate, capryloylglycine, 4-ethylphenylsulfate, and azelaic acid were found to be decreased. Collectively, the metabolomic profiling has uncovered distinct metabolic signatures in patients with acute myocarditis. The amino acid metabolism appears to play a pivotal role in the pathogenesis of acute myocarditis, offering potential avenues for diagnostic and therapeutic development.

摘要

急性心肌炎以炎症性心肌损伤为特征,存在发生心力衰竭和猝死的重大风险。尽管其病情严重,但缺乏特异性生物标志物。本研究使用超高效液相色谱-串联质谱法(UPLC-MS/MS)对21例急性心肌炎患者和21例对照的尿液样本进行代谢组学分析,发现患者中有728种代谢物增加,820种代谢物减少。受影响的途径主要与氨基酸代谢、脂质代谢、碳水化合物代谢、核苷酸代谢等有关。我们已经验证了19种代谢物,其受试者工作特征曲线下面积(AUC-ROC)大于0.7且鉴定置信度高。急性心肌炎患者中上调的潜在生物标志物包括植物鞘氨醇、N-乙酰神经氨酸、吲哚乳酸、L-谷氨酸、4-吡哆酸、N1-甲基-2-吡啶酮-5-甲酰胺、棕榈酸、羟基苯乳酸、核黄素、烟酸、胆碱、N-甲酰犬尿氨酸、鸟嘌呤和次黄嘌呤。相反,发现癸二酸、4-乙烯基苯酚硫酸盐、辛酰甘氨酸、4-乙基苯硫酸盐和壬二酸减少。总体而言,代谢组学分析揭示了急性心肌炎患者独特的代谢特征。氨基酸代谢似乎在急性心肌炎的发病机制中起关键作用,为诊断和治疗的发展提供了潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/3238f3d0d229/41598_2025_93655_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/392e5b3fd02c/41598_2025_93655_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/e9018fb5ba13/41598_2025_93655_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/172747456e88/41598_2025_93655_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/f803d1b2bdbc/41598_2025_93655_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/3238f3d0d229/41598_2025_93655_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/392e5b3fd02c/41598_2025_93655_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/e9018fb5ba13/41598_2025_93655_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/440c88d5fdc3/41598_2025_93655_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/172747456e88/41598_2025_93655_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/f803d1b2bdbc/41598_2025_93655_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b0d/11920081/3238f3d0d229/41598_2025_93655_Fig6_HTML.jpg

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