游离Sema7a促进小鼠急性肺炎加速消退的作用机制研究*

doi:10.3969/j.issn.1671-2587.2025.04.002

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (4): 442-450.DOI: 10.3969/j.issn.1671-2587.2025.04.002

游离Sema7a促进小鼠急性肺炎加速消退的作用机制研究^*

伍忆倩¹, 肖倩¹, 苑召虎², 佐妍¹, 陈雄燕¹, 宁伟¹

¹桂林市人民医院,广西桂林 541002;
²广州市第一人民医院,广东广州 510180

收稿日期:2025-04-27 出版日期:2025-08-20 发布日期:2025-08-22
通讯作者: 肖倩,主要从事输血治疗方面研究,（E-mail）2058883683@qq.com。
作者简介:伍忆倩,主要从事输血医学方面研究,（E-mail）2276198288@qq.com。
基金资助:
*本课题受桂林市科技局桂林市科学研究与技术开发计划项目（No.20232E35-23）、广东省基础与应用基础研究基金项目（No.2022A1515220019）资助

Study on the Mechanism of Soluble Sema7a in Accelerating the Resolution of Acute Pneumonia in Mice

WU Yiqian¹, XIAO Qian¹, YUAN Zhaohu², ZUO Yan¹, CHEN Xiongyan¹, NING Wei¹

¹Department of Blood Transfusion, Guilin People's Hospital, Guilin, 541002;
²Department of Blood Transfusion, Guangzhou First Peoples Hospital, Guangzhou 510180

Received:2025-04-27 Online:2025-08-20 Published:2025-08-22

摘要/Abstract

摘要： 目的探究Sema7a促进急性肺炎炎症消退的分子机制。方法本研究采用Sema7a-eKO基因敲除小鼠模型、HE染色、ELISA检测及蛋白质组学分析等新技术在分子、组织及动物三个水平上,探明了游离Sema7a在调节急性肺炎小鼠模型中巨噬细胞代谢重编程,促进巨噬细胞向M2分化,加速炎症消退及促进肺组织恢复稳态中的作用。结果 Sema7a-/-及Sema7a+/+肺炎小鼠模型显示在24、48、72和96 h时两组小鼠肺泡结构均有不同程度的破坏。与Sema7a+/+小鼠相比,Sema7a-/-小鼠肺组织浸润更多的中性粒细胞及红细胞,肺泡结构破坏更明显,且表现出更强的中性粒细胞浸润及更长的消退间隔（26.2 h vs.13.8 h,P<0.05）;ELISA分析显示在第48 h时,Sema7a-/-小鼠肺泡灌洗液中IL-6、KC、TNF-α和IL-1β显著高于Sema7a+/+对照组小鼠（P均<0.05）;我们通过5D Label-free蛋白质组学技术明确了Sema7a处理后MΦs中101 320个肽段和7 357个蛋白质的变化,GO二级功能注释分析显示巨噬细胞生物进程有59个蛋白质分子的变化与其细胞变化过程相关,52个蛋白质分子的变化与生物学功能的调节相关,37个蛋白质分子的变化与其代谢过程相关（P均<0.05）;KEGG通路注释和富集分析显示线粒体呼吸链信号通路变化显著,Sema7a刺激后MΦs表面的M1标记物（STAT-1,CD40,CD80）和炎症细胞因子显著降低,而M2标记物（Arg1、CD163和CD20）和IL-10在蛋白水平显著增加。结论游离Sema7a蛋白可通过调节急性肺炎模型中巨噬细胞代谢重编程增强其氧化磷酸化水平,促进巨噬细胞向M2型细胞分化,进而促进肺部炎症消退,最终使肺组织恢复稳态。

关键词: 急性肺炎, Sema7a, 巨噬细胞, 蛋白质组学, 细胞因子

Abstract: Objective To elucidate the molecular mechanisms by which Sema7a promotes inflammatory regression in acute pneumonia. Methods We investigated the role of soluble Sema7a in regulating macrophage metabolic reprogramming, promoting M2 polarization, accelerating inflammation resolution, and facilitating pulmonary homeostasis in a mouse model of acute pneumonia by employing Sema7a-eKO knockout mice, HE staining, ELISA, and advanced proteomic analyses. Results Both Sema7a-/- and Sema7a+/+ pneumonia models exhibited different degrees of destruction of alveolar structures in both groups at 24, 48, 72, and 96 h. Notably, Sema7a-/- mice displayed exacerbated more neutrophil/erythrocyte infiltration and more severe alveolar destruction compared to Sema7a+/+ mice. Sema7a-/- mice demonstrated prolonged resolution intervals (26.2 h vs. 13.8 h, P<0.05) and significantly elevated IL-6, KC, TNF-α, and IL-1β levels in bronchoalveolar lavage fluid at 48 h (P<0.05). 5D Label-free proteomic analysis revealed 101 320 peptide fragments and 7 357 protein alterations in Sema7a-treated macrophages. 59 proteins were associated with cellular processes, 52 with biological regulation, and 37 with metabolic processes (all P<0.05). Mitochondrial respiratory chain signaling showed significant modulation. Sema7a downregulated M1 markers (STAT-1, CD40, CD80) and pro-inflammatory cytokines while upregulating M2 markers (Arg1, CD163, CD206) and IL-10 at the protein level. Conclusion In an acute pneumonia model, soluble Sema7a protein can enhance mitochondrial oxidative phosphorylation through macrophage metabolic reprogramming, which drives M2 polarization, accelerates inflammatory cell clearance, and ultimately restores pulmonary homeostasis.

Key words: Acute pneumonia, Sema7a, Macrophages, Proteomics, Cytokine

中图分类号:

R563.1

伍忆倩, 肖倩, 苑召虎, 佐妍, 陈雄燕, 宁伟. 游离Sema7a促进小鼠急性肺炎加速消退的作用机制研究^*[J]. 临床输血与检验, 2025, 27(4): 442-450.

WU Yiqian, XIAO Qian, YUAN Zhaohu, ZUO Yan, CHEN Xiongyan, NING Wei. Study on the Mechanism of Soluble Sema7a in Accelerating the Resolution of Acute Pneumonia in Mice[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(4): 442-450.

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游离Sema7a促进小鼠急性肺炎加速消退的作用机制研究^*

Study on the Mechanism of Soluble Sema7a in Accelerating the Resolution of Acute Pneumonia in Mice

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