中性粒细胞胞外陷阱在溃疡性结肠炎中的作用  

The role of neutrophil extracellular traps in ulcerative colitis

作　　者：孟秋月 袁一帆 李娜[1,2] 卢嘉莉 叶梅 MENG Qiuyue;YUAN Yifan;LI Na;LU Jiali;YE Mei(Department of Gastroenterology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases,Hubei Key Laboratory of Intestinal and Colorectal Diseases,Wuhan 430071,China;Department of Gerontology and Geriatrics,West China Hospital,Sichuan University,China National Clinical Research Center for Geriatric Medicine,Chengdu 610041,China)

机构地区：[1]武汉大学中南医院消化内科,武汉430071 [2]湖北省肠道与结肠疾病临床研究中心/湖北省肠道与结肠疾病重点实验室,武汉430071 [3]四川大学华西医院老年病科/国家老年疾病临床医学研究中心,成都610041

出　　处：《医学新知》2025年第3期289-302,I0003-I0007,共19页New Medicine

基　　金：国家自然科学基金面上项目(82470556)。

摘　　要：目的探究中性粒细胞胞外陷阱(neutrophil extracellular traps,NETs)在溃疡性结肠炎(ulcerative colitis,UC)中的作用机制。方法从GEO数据库下载UC患者和正常对照的RNA数据,筛选差异表达基因,将筛选的基因与先前报道的NETs相关基因相交,用于GO、KEGG和GSEA等功能富集分析。利用机器学习确定关键基因,以进一步分析免疫浸润和生物功能。基于关键基因构建诊断模型,并进行外部数据集验证,鉴定NETs相关分子亚型,利用DGIdb数据库预测靶向关键基因的药物。结果共筛选出38个NETs相关的差异表达基因,F3、MME、PTAFR和SLC25A37为关键基因,这些基因的mRNA表达水平升高,与炎症信号通路有关,显示出良好的诊断效能。鉴定出的两种独特NETs相关分子亚型展现出不同的免疫特性和临床特征。22种靶向关键基因的药物可能成为UC的潜在治疗药物。结论NETs在UC患者中表达升高,在疾病发生发展过程中起促炎作用。F3、MME、PTAFR和SLC25A37关键基因可能参与UC的病理过程,鉴定出的两个NETs亚型可为UC的临床治疗提供一定参考。Objective To investigate the role of neutrophil extracellular traps(NETs)in the pathogenesis of ulcerative colitis(UC).Methods RNA data from UC patients and normal controls were downloaded from the GEO database to screen for differential expression genes(DEGs),intersecting the screened genes with previously reported NETs-associated genes for functional enrichment assays such as GO,KEGG,and GSEA.Use machine learning to identify key genes for further analysis of immune infiltration and biological function.Diagnostic models were constructed based on key genes and validated against external data sets,and NETs associated molecular subtypes were identified.Prediction of drugs targeting key genes using DGIdb database.Results A total of 38 NETs-related DEGs were screened.F3,MME,PTAFR,and SLC25A37 were identified as key genes,with elevated levels of mRNA expression,and were associated with inflammatory signaling pathways and exhibited remarkable diagnostic efficacy.Two unique NETs-related subtypes derived from key genes had distinct immune and clinical characteristics.22 targeted drugs might become potential therapeutic agents for UC.Conclusion NETs expression is elevated in UC patients and plays a pro-inflammatory role in disease progression.F3,MME,PTAFR,and SLC25A37 were identified as potential contributors to the pathogenesis of UC.The two identified subtypes of NETs can provide some reference for the clinical treatment of UC.

关 键 词：中性粒细胞胞外陷阱 溃疡性结肠炎 转录组测序 机器学习 分子亚型 

分 类 号：R574.62[医药卫生—消化系统]