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COVID-19 患者尿液神经鞘脂和甘油磷脂水平的动态变化及其与 COVID-19 相关肾损伤的相关性。

Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries.

机构信息

Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.

Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.

出版信息

J Biomed Sci. 2022 Nov 10;29(1):94. doi: 10.1186/s12929-022-00880-5.

Abstract

BACKGROUND

Among various complications of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), renal complications, namely COVID-19-associated kidney injuries, are related to the mortality of COVID-19.

METHODS

In this retrospective cross-sectional study, we measured the sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties, using liquid chromatography-mass spectrometry in 272 urine samples collected longitudinally from 91 COVID-19 subjects and 95 control subjects without infectious diseases, to elucidate the pathogenesis of COVID-19-associated kidney injuries.

RESULTS

The urinary levels of C18:0, C18:1, C22:0, and C24:0 ceramides, sphingosine, dihydrosphingosine, phosphatidylcholine, lysophosphatidylcholine, lysophosphatidic acid, and phosphatidylglycerol decreased, while those of phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, and lysophosphatidylethanolamine increased in patients with mild COVID-19, especially during the early phase (day 1-3), suggesting that these modulations might reflect the direct effects of infection with SARS-CoV-2. Generally, the urinary levels of sphingomyelin, ceramides, sphingosine, dihydrosphingosine, dihydrosphingosine L-phosphate, phosphatidylcholine, lysophosphatidic acid, phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylglycerol, lysophosphatidylglycerol, phosphatidylinositol, and lysophosphatidylinositol increased, especially in patients with severe COVID-19 during the later phase, suggesting that their modulations might result from kidney injuries accompanying severe COVID-19.

CONCLUSIONS

Considering the biological properties of sphingolipids and glycerophospholipids, an understanding of their urinary modulations in COVID-19 will help us to understand the mechanisms causing COVID-19-associated kidney injuries as well as general acute kidney injuries and may prompt researchers to develop laboratory tests for predicting maximum severity and/or novel reagents to suppress the renal complications of COVID-19.

摘要

背景

由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)的各种并发症中,肾脏并发症,即 COVID-19 相关的肾损伤,与 COVID-19 的死亡率有关。

方法

在这项回顾性的横断面研究中,我们使用液相色谱-质谱法测量了 272 份尿液样本中的鞘脂和甘油磷脂,这些样本是从 91 名 COVID-19 患者和 95 名无传染病的对照患者中纵向收集的,以阐明 COVID-19 相关肾损伤的发病机制。

结果

轻度 COVID-19 患者(尤其是早期[第 1-3 天])的尿中 C18:0、C18:1、C22:0 和 C24:0 神经酰胺、神经鞘氨醇、二氢神经鞘氨醇、磷脂酰胆碱、溶血磷脂酰胆碱、溶血磷脂酸和磷脂酰甘油水平降低,而丝氨酸磷脂、溶血丝氨酸磷脂、磷脂乙醇胺和溶血磷脂乙醇胺水平升高,提示这些变化可能反映了 SARS-CoV-2 感染的直接作用。一般来说,尿中鞘磷脂、神经酰胺、神经鞘氨醇、二氢神经鞘氨醇、二氢神经鞘氨醇 L-磷酸、磷脂酰胆碱、溶血磷脂酸、丝氨酸磷脂、溶血丝氨酸磷脂、磷脂乙醇胺、溶血磷脂乙醇胺、磷脂酰甘油、溶血磷脂酰甘油、磷脂酰肌醇和溶血磷脂酰肌醇水平升高,尤其是在重度 COVID-19 患者的后期,提示这些变化可能是由重度 COVID-19 伴发的肾损伤所致。

结论

考虑到鞘脂和甘油磷脂的生物学特性,了解它们在 COVID-19 中的尿调节情况,有助于我们了解导致 COVID-19 相关肾损伤以及一般急性肾损伤的机制,并可能促使研究人员开发用于预测最大严重程度和/或新型试剂以抑制 COVID-19 肾脏并发症的实验室检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e101/9648042/c8325fb6260d/12929_2022_880_Fig1_HTML.jpg

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