新冠病毒患者细胞外和细胞内氧化还原状态的新见解。

New insights into extracellular and intracellular redox status in COVID-19 patients.

机构信息

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Redox Biol. 2023 Feb;59:102563. doi: 10.1016/j.redox.2022.102563. Epub 2022 Dec 2.

DOI:10.1016/j.redox.2022.102563

PMID:36493512

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9715463/

Abstract

BACKGROUND

The imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients.

METHOD

The multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls. Top genes were designated based on the degree and closeness centralities. The expression of high-ranked genes was evaluated in PBMCs and nasopharyngeal (NP) samples of 30 COVID-19 patients and 30 healthy controls. The intracellular levels of GSH and ROS/O - and extracellular oxidative stress markers were assayed in PBMCs and plasma samples by flow cytometry and ELISA. ELISA results were applied to construct a classification model using logistic regression to differentiate COVID-19 patients from healthy controls.

RESULTS

CAT, NFE2L2, SOD1, SOD2 and CYBB were 5 top genes in the network analysis. The expression of these genes and intracellular levels of ROS/O were increased in PBMCs of COVID-19 patients while the GSH level decreased. The expression of high-ranked genes was lower in NP samples of COVID-19 patients compared to control group. The activity of extracellular enzymes CAT and SOD, and the total oxidant status (TOS) level were increased in plasma samples of COVID-19 patients. Also, the 2-marker panel of CAT and TOS and 3-marker panel showed the best performance.

CONCLUSION

SARS-COV-2 disrupts the redox equilibrium in immune cells and the upper respiratory tract, leading to exacerbated inflammation and increased replication and entrance of SARS-COV-2 into host cells. Furthermore, utilizing markers of oxidative stress as a complementary validation to discriminate COVID-19 from healthy controls, seems promising.

摘要

背景

氧化还原平衡失调会导致病毒感染时发生过度炎症。在这项研究中，我们探索了针对 SARS-CoV-2 感染的氧化还原系统特征，并检查了 COVID-19 患者中外周血单个核细胞（PBMC）中这些细胞内外特征的状态。

方法

使用来自 GSE164805 的与氧化应激相关的生物过程、蛋白质-蛋白质相互作用、转录因子和共表达系数的多水平数据构建多水平网络，其中包括 COVID-19 患者和健康对照者的 PBMC 基因表达谱。根据节点的度数和接近度来指定高排名基因。评估了 30 名 COVID-19 患者和 30 名健康对照者的 PBMC 和鼻咽（NP）样本中高排名基因的表达。使用流式细胞术和 ELISA 测定 PBMC 和血浆样本中 GSH 和 ROS/O-的细胞内水平以及氧化应激的细胞外标记物。使用逻辑回归对 ELISA 结果进行分析，以构建一个分类模型，从而将 COVID-19 患者与健康对照者区分开来。

结果

网络分析中前 5 个基因是 CAT、NFE2L2、SOD1、SOD2 和 CYBB。COVID-19 患者 PBMC 中这些基因的表达和 ROS/O-的细胞内水平增加，而 GSH 水平降低。与对照组相比，COVID-19 患者的 NP 样本中高排名基因的表达水平较低。COVID-19 患者血浆样本中细胞外酶 CAT 和 SOD 的活性以及总氧化剂状态（TOS）水平增加。此外，CAT 和 TOS 的 2 标志物面板和 3 标志物面板表现最佳。