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南京医科大学学报(自然科学版) 第45卷第6期
·786 · Journal of Nanjing Medical University(Natural Sciences) 2025年6月
·基础研究·
scRNA⁃seq 和 Bulk RNA⁃seq 联合分析揭示 MTRNR2L1 介导
COPD进展中PANoptosis下调
戈艳蕾 ,孙思怡 ,任泓沁 ,姚雪鑫 ,赵 倩 ,李文强 ,陈伟彬 ,白 静 ,喻昌利 ,董爱英 ,刘铁军 ,付爱双 1*
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华北理工大学附属医院呼吸与危重症医学科,河北 唐山 063000;自贡市第一人民医院呼吸与危重症医学科,四川 自
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贡 643000;华北理工大学附属医院CT室,重症医学科,微生物室,麻醉科,河北 唐山 063000
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[摘 要] 目的:探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)发展过程中 MT⁃RNR2 样蛋白 1(MT⁃
RNR2 like protein 1,MTRNR2L1)介导的泛凋亡(PANoptosis)调控机制,为寻找 COPD 发病机制提供新思路。方法:通过基因表
达综合数据库(Gene Expression Omnibus,GEO)中COPD患者的批量RNA测序(Bulk RNA sequencing,Bulk RNA⁃seq)数据和单
细胞RNA 测序(single cell RNA sequencing,scRNA⁃Seq)数据探究COPD 患者肺组织中细胞构成,并分析细胞参与疾病发生的
相关通路。在烟雾/脂多糖(lipopolysaccharide,LPS)暴露的小鼠中模拟PANoptosis,评估MTRNR2L1和PANoptosis 蛋白表达情
况,明确其在COPD发生发展中的作用。结果:Bulk RNA⁃seq显示COPD患者T细胞反应相关基因的表达变化。scRNA⁃Seq证
实与对照组相比,COPD组的CD8 T细胞数减少,上皮细胞数增加;MTRNR2L1在COPD患者的免疫细胞和上皮细胞中表达水
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平上调;COPD患者肺组织、CD8 T 细胞和上皮细胞中的 PANoptosis 相关基因表达水平降低。暴露于烟雾/LPS的小鼠肺表现
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出肺泡损伤、PANoptosis 蛋白表达上调,MTRNR2L1 过表达显著抑制细胞 PANoptosis 并下调 ZBP1、Caspase⁃3、GSDMD 和
MLKL 的水平。结论:CD8 T 细胞与上皮细胞的差异表达基因分别在泛凋亡相关通路富集,提示PANoptosis参与 COPD 的发
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生发展,COPD 发病过程中PANoptosis 与PANoptosis 蛋白表达增高相关,MTRNR2L1对PANoptosis 有抑制作用,调节PANopto⁃
sis可能为减轻肺损伤和改善肺通气功能提供新的治疗机会。
[关键词] 慢性阻塞性肺疾病;肺损伤;PANoptosis;单细胞RNA测序;批量RNA测序
[中图分类号] R563.9 [文献标志码] A [文章编号] 1007⁃4368(2025)06⁃786⁃12
doi:10.7655/NYDXBNSN240702
Combined analysis of scRNA⁃seq and Bulk RNA⁃seq revealed that MTRNR2L1 mediated
the downregulation of PANoptosis in COPD
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GE Yanlei ,SUN Siyi ,REN Hongqin ,YAO Xuexin ,ZHAO Qian ,LI Wenqiang ,CHEN Weibin ,BAI Jing ,YU
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Changli ,DONG Aiying ,LIU Tiejun ,FU Aishuang 1*
Department of Respiratory and Critical Care Medicine,North China University of Science and Technology Affiliated
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Hospital,Tangshan 063000;Department of Respiratory and Critical Care Medicine,Zigong First People’s Hospital,
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Zigong,643000;Department of CT Lab,Department of Intensive Care Unit,Department of Clinical Microbiology
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Laboratory,Department of Anesthesiology,North China University of Science and Technology Affiliated Hospital,
Tangshan 063000,China
[Abstract] Objective:To explore the mechanism of MT⁃RNR2⁃like protein 1(MTRNR2L1)⁃mediated regulation of PANoptosis
during the development of chronic obstructive pulmonary disease(COPD),and to provide new ideas for finding the pathogenesis of
COPD. Methods:Bulk RNA sequencing(Bulk RNA⁃seq)data and single cell RNA sequencing(scRNA⁃Seq)data from COPD patients
in Gene Expression Omnibus(GEO)were used to explore the cellular composition in COPD patients’lung tissues and to analyze the
pathways involved in the development of the disease. PANoptosis was simulated in smoke/lipopolysaccharide(LPS)⁃exposed mice,and
MTRNR2L1 and PANoptosis protein expression levels were assessed to clarify their roles in the development of COPD. Results:Bulk
[基金项目] 唐山市人才资助项目(C202303026)
通信作者(Corresponding author),E⁃mail:maxfas@163.com(ORCID:0000⁃0003⁃2840⁃4042)
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