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新生儿坏死性小肠结肠炎氧化应激谱的综合表征

Comprehensive Characterization of the Oxidative Stress Profiles in Neonatal Necrotizing Enterocolitis.

作者信息

Xiong Xiaofeng, Wu Luyao, Liu Xin, Wang Jing, Xiao Jun, Chen Ke, Zhuansun Didi, Meng Xinyao, Feng Jiexiong, Chen Xuyong

机构信息

Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hubei Clinical Center of Hirschsprung disease and allied disorders, Wuhan, China.

出版信息

Int J Med Sci. 2025 Apr 9;22(9):2139-2154. doi: 10.7150/ijms.109008. eCollection 2025.

DOI:10.7150/ijms.109008
PMID:40303487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12035842/
Abstract

This study aims to portray the characteristics of oxidative stress (OS) in cases of Necrotizing enterocolitis (NEC), identify the hub genes and associated mechanisms involved, and explore potential drugs for NEC. We performed a comprehensive analysis integrating bulk-RNA sequencing and single-cell RNA sequencing datasets, coupled with various techniques including differential analysis, gene set enrichment analysis, and immune infiltration analysis. We aimed to systematically elucidate the variations in functions related to OS among distinct cell populations within both NEC and non-NEC tissues. Additionally, we depicted the longitudinal changes in immune cells, with a particular focus on macrophages, throughout the progression of NEC. NEC mice model was established and RT-qPCR was performed to validate the expression of the hub genes. In total, 465 OS related genes were found, and 53 of them were significantly differentially expressed. These genes were mainly involved in several signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, FOXO signaling pathway, inflammatory bowel disease. The top 10 hub genes were , , , , , , , , and . Ten kinds of drug were discovered as the potential treatment for NEC. Four specific macrophages subtypes and relative function were identified in NEC. RT-qPCR and immunofluorescence staining confirmed the expression of the hub genes in NEC model. This investigation yielded innovative insights into the immune environment and therapeutic methodologies directed at oxidative stress in the pathogenesis of NEC.

摘要

本研究旨在描绘坏死性小肠结肠炎（NEC）病例中氧化应激（OS）的特征，识别其中涉及的关键基因和相关机制，并探索针对NEC的潜在药物。我们进行了一项综合分析，整合了批量RNA测序和单细胞RNA测序数据集，并结合了差异分析、基因集富集分析和免疫浸润分析等多种技术。我们旨在系统地阐明NEC和非NEC组织中不同细胞群体之间与OS相关的功能变化。此外，我们描绘了NEC进展过程中免疫细胞的纵向变化，特别关注巨噬细胞。建立了NEC小鼠模型，并进行了RT-qPCR以验证关键基因的表达。总共发现了465个与OS相关的基因，其中53个基因有显著差异表达。这些基因主要参与几种信号通路，如TNF信号通路、IL-17信号通路、FOXO信号通路、炎症性肠病。排名前十的关键基因是 、 、 、 、 、 、 、 、 和 。发现了十种药物作为NEC的潜在治疗方法。在NEC中鉴定出四种特定的巨噬细胞亚型及其相关功能。RT-qPCR和免疫荧光染色证实了关键基因在NEC模型中的表达。这项研究为NEC发病机制中针对氧化应激的免疫环境和治疗方法提供了创新性见解。

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本文引用的文献

1
Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives.深入探究坏死性小肠结肠炎：连接临床、微生物和分子层面的观点
Gut Microbes. 2025 Dec;17(1):2451071. doi: 10.1080/19490976.2025.2451071. Epub 2025 Jan 18.
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Redox Chemistry: Implications for Necrotizing Enterocolitis.氧化还原化学：对坏死性小肠结肠炎的影响。
Int J Mol Sci. 2024 Aug 1;25(15):8416. doi: 10.3390/ijms25158416.
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The severity of NEC is ameliorated by prostaglandin E2 through regulating intestinal microcirculation.前列腺素 E2 通过调节肠道微循环改善 NEC 的严重程度。
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NAMPT inhibition relieves intestinal inflammation by regulating macrophage activation in experimental necrotizing enterocolitis.NAMPT 抑制通过调节实验性坏死性小肠结肠炎中的巨噬细胞活化来缓解肠道炎症。
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How to place the duality of specific MMP-9 inhibition for treatment of inflammatory bowel diseases into clinical opportunities?如何将特异性 MMP-9 抑制的双重性转化为治疗炎症性肠病的临床机会？
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