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新冠病毒感染相关血栓形成中脂质介质和氧化脂质的分析

Profiling of lipid mediators and oxylipins in SARS-CoV-2 infection associated thrombosis.

作者信息

Peng Daibao, Chen Fei, Sun Haixuan, Xia Mao

机构信息

Department of Clinical Laboratory Medicine, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Department of Clinical Laboratory, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, China.

出版信息

Sci Rep. 2025 Aug 29;15(1):31904. doi: 10.1038/s41598-025-17722-7.

DOI:10.1038/s41598-025-17722-7
PMID:40883531
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12397397/
Abstract

Thrombosis is a life-threatening complication in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study aims to conduct a statistical analysis of the incidence of blood clots and lipid concentrations, and to examine the networks of oxylipins in hospitalised patients with SARS-CoV-2. Serum samples of 1731 hospitalised patients with SARS-COV-2 were used to measure six lipid parameters: total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (apoA), and apolipoprotein B (apoB). Additionally, the lipid profiles and oxidative lipidomics characteristics were examined via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) in SARS-COV-2-positive patients with and without thrombosis. The mortality rate in the SARS-COV-2 thrombosis group was significantly higher at 29.6% compared to the SARS-COV-2 non-thrombosis group at 12.1% (P < 0.0001). The levels of the lipid parameters were closely associated with both thrombosis and SARS-COV-2 severity. Patients with SARS-COV-2 admitted to the hospital exhibited significant changes in oxidative lipid metabolites, specifically in the arachidonic acid (ARA) and docosahexaenoic acid (DHA) classes, compared with those in the control group. Among the thrombus group, 28 oxidative lipid metabolites were found to be differentially expressed compared to the non-thrombus group, and with the most notable variations observed in 20-hydroxyPGF2α and 14(15)-EpETE. Enrichment analysis using KEGG revealed that differential oxidized lipid metabolites mainly concentrated in the ARA and serotonergic synapses metabolism signaling pathway. Our findings indicate a close association between lipid mediators and both SARS-COV-2 and thrombi. Specifically, ARA and serotonergic synapses metabolism signaling pathway may be an important pathogenic factor for thrombosis caused by SARS-COV-2. Furthermore, 20-hydroxyPGF2α and 14(15)-EpETE show promise as potential biomarkers for SARS-CoV-2-induced thrombosis.

摘要

血栓形成是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染中一种危及生命的并发症。本研究旨在对住院的SARS-CoV-2患者的血栓发生率和血脂浓度进行统计分析,并研究氧化脂质网络。1731例住院的SARS-CoV-2患者的血清样本用于测量六个脂质参数:总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(apoA)和载脂蛋白B(apoB)。此外,通过液相色谱-电喷雾电离-串联质谱(LC-MS/MS)对有血栓形成和无血栓形成的SARS-CoV-2阳性患者的血脂谱和氧化脂质组学特征进行了检测。SARS-CoV-2血栓形成组的死亡率显著高于SARS-CoV-2非血栓形成组,分别为29.6%和12.1%(P<0.0001)。脂质参数水平与血栓形成和SARS-CoV-2严重程度密切相关。与对照组相比,住院的SARS-CoV-2患者的氧化脂质代谢产物出现了显著变化,特别是花生四烯酸(ARA)和二十二碳六烯酸(DHA)类。在血栓组中,发现与非血栓组相比有28种氧化脂质代谢产物差异表达,其中20-羟基PGF2α和14(15)-EpETE的变化最为显著。使用KEGG进行的富集分析表明,差异氧化脂质代谢产物主要集中在ARA和5-羟色胺能突触代谢信号通路。我们的研究结果表明脂质介质与SARS-CoV-2和血栓之间存在密切关联。具体而言,ARA和5-羟色胺能突触代谢信号通路可能是SARS-CoV-2导致血栓形成的重要致病因素。此外,20-羟基PGF2α和14(15)-EpETE有望作为SARS-CoV-2诱导血栓形成的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d0/12397397/f7348e13b832/41598_2025_17722_Fig6_HTML.jpg
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