Article record

SIRT3下调激活巨噬细胞促炎功能并加重慢性鼻窦炎小鼠模型中的嗅觉丧失

Downregulation of SIRT3 Activates Macrophage Proinflammatory Function and Exacerbates Olfactory Loss in a Mouse Model of Chronic Rhinosinusitis.

基础研究鼻科IF 11.6Q1

文献信息

PMID	42950956
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Tianyu Wang 查看其他 24 位作者 Jianyu Yan；Yin Cheng；Xudong Cha；Fengzhen Li；Tengfei Li；Boyu Cai；Mengxia Zhou；Caiquan Liang；Zhe Wang；Penghui Fu；Shenglei Wang；Yingqi Xie；Changhai Xiong；Zengyi Xu；Li Chen；Aonan Gao；Zhennan Qu；Yajing Zhu；Yiqun Yu；Chunlin Zhuang；Enhao Wang；Hu Peng；Wenwen Ren；Huanhai Liu
作者单位	Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Naval Medical University/Second Military Medical University, Shanghai 200433, China. 查看其他 8 条单位信息 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Naval Medical University/Second Military Medical University, Shanghai 200433, China.；Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.；Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Department of ORL-HNS, Shanghai Fourth People's Hospital, and School of Medicine, Tongji University, 200434 Shanghai, China.；ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Olfactory Disorder Diagnosis and Treatment Center, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.；Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: enhaowang1995@163.com.；Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: penghudy@126.com.；Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: wenwenren@smmu.edu.cn.；Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China. Electronic address: liuhuanhaiok@smmu.edu.cn.
期刊	The Journal of allergy and clinical immunology
SCI 分区	Q1
IF	11.6
研究类型	基础研究 · 基础／转化
所属专科	鼻科

中文摘要

背景： 嗅觉黏膜的炎症而非气流阻塞，是伴嗅觉功能障碍的慢性鼻窦炎（CRSwOD）中嗅觉恢复的主要障碍。巨噬细胞是嗅觉黏膜中占主导地位的免疫细胞群，在调节局部炎症和嗅觉神经再生中发挥关键作用。
目的： 本研究旨在探讨Sirtuin 3（SIRT3）在调节巨噬细胞功能中的作用及其对CRSwOD嗅觉恢复的影响。
方法： 分析单细胞RNA测序、批量RNA测序和非靶向代谢组学数据，以表征CRSwOD中的免疫和神经元改变，重点关注巨噬细胞活化状态。使用SIRT3缺陷小鼠进行体内实验以评估嗅觉感觉神经元（OSN）完整性，同时通过体外实验检查炎症条件下SIRT3缺陷巨噬细胞的代谢和炎症特征。
结果： 转录组分析显示，嗅觉功能障碍与黏膜巨噬细胞功能状态改变密切相关。在小鼠慢性鼻窦炎进展过程中，SIRT3缺失加剧了OSN丢失，并损害了巨噬细胞维持神经元稳态的保护作用。机制上，SIRT3缺陷增强了巨噬细胞促炎活性，增加了缺氧诱导因子1α（HIF-1α）表达，促进了糖酵解，并降低了线粒体膜电位。
结论： 在慢性鼻窦炎小鼠模型中，SIRT3调节嗅觉黏膜内巨噬细胞介导的炎症代谢，从而防止炎症诱导的嗅觉损伤。这些发现为炎症驱动的嗅觉功能障碍提供了机制见解，并将SIRT3确定为CRSwOD的潜在治疗靶点。

英文摘要

BACKGROUND: Inflammation of the olfactory mucosa, rather than airflow obstruction, is a major barrier to olfactory recovery in chronic rhinosinusitis with olfactory dysfunction (CRSwOD). Macrophages, a predominant immune cell population in the olfactory mucosa, play a key role in regulating local inflammation and olfactory neuroregeneration.
OBJECTIVE: This study aimed to investigate the role of Sirtuin 3 (SIRT3) in modulating macrophage function and its impact on olfactory recovery in CRSwOD.
METHODS: Single-cell RNA sequencing, bulk RNA sequencing, and untargeted metabolomics data were analyzed to characterize immune and neuronal alterations in CRSwOD, with a focus on macrophage activation states. In vivo experiments using SIRT3-deficient mice were performed to evaluate olfactory sensory neuron (OSN) integrity, while in vitro assays examined the metabolic and inflammatory profiles of SIRT3-deficient macrophages under inflammatory conditions.
RESULTS: Transcriptomic analysis revealed that olfactory dysfunction was closely associated with the altered functional status of mucosal macrophages. During the progression of chronic rhinosinusitis in mice, loss of SIRT3 exacerbated OSN loss and impaired the protective role of macrophages in maintaining neuronal homeostasis. Mechanistically, SIRT3 deficiency enhanced macrophage proinflammatory activity, increased hypoxia-inducible factor 1α (HIF-1α) expression, promoted glycolysis, and reduced mitochondrial membrane potential.
CONCLUSION: In a mouse model of chronic rhinosinusitis, SIRT3 modulates macrophage-mediated inflammatory metabolism within the olfactory mucosa, thereby protecting against inflammation-induced olfactory damage. These findings provide mechanistic insight into inflammation-driven olfactory dysfunction and identify SIRT3 as a potential therapeutic target for CRSwOD.