活性氧在过敏性鼻炎中作用的叙述性综述

文献信息

中文摘要

背景： 过敏性鼻炎（AR）的研究日益认识到，活性氧（ROS）不仅仅是氧化代谢的副产物，而是在该疾病发病过程中作为2型炎症网络的调节因子发挥作用。本叙述性综述通过分析探讨全身氧化应激标志物、上皮屏障功能障碍、免疫细胞来源的ROS、线粒体氧化还原信号以及炎症小体相关通路的研究，总结了ROS在AR病理生理学中的作用。方法：我们对文献进行了结构化检索，审查了五个主要数据库（PubMed、Scopus、EMBASE、Cochrane Library和Google Scholar），并确定了17项发表于2000年至2026年间的符合条件的研究。结果：临床研究表明，AR患者表现出全身氧化还原稳态改变，包括硫醇-二硫化物失衡和脂质过氧化增加。然而，这些发现主要来自外周血标志物的测量，而非鼻黏膜。实验研究一致表明，过敏原暴露增加了鼻上皮细胞和免疫细胞中的ROS水平，破坏了上皮屏障，下调了紧密连接蛋白，并激活了炎症信号通路。尽管直接的鼻组织数据仍然有限，但从外周血和支气管激发模型推断的证据表明，嗜酸性粒细胞和中性粒细胞在过敏反应晚期阶段促进ROS的产生，从而可能放大和维持气道炎症。还有证据表明，线粒体ROS和DUOX依赖性信号传导导致上皮功能障碍，包括释放损伤相关分子模式和激活炎症小体通路。与此同时，抗氧化防御机制，如KEAP1/NRF2轴和线粒体自噬相关通路，似乎通过维持氧化还原稳态来调节疾病严重程度。结论：诸如ROS清除剂和氧化应激响应性药物递送系统等实验策略在临床前和初步研究中已显示出早期概念验证潜力，但在考虑任何临床应用之前，严格且大规模临床支持是绝对必要的。总体而言，当前证据表明，ROS在AR中作为情境依赖性氧化还原介质发挥作用，而非作为主要原因。ROS的生物学效应似乎取决于合成部位、亚细胞定位以及氧化剂产生与抗氧化防御之间的平衡。需要进一步直接评估鼻黏膜ROS动态的研究和精心设计的临床试验，以阐明这些研究的转化相关性以及不同AR治疗方法的治疗潜力。

英文摘要

Studies of allergic rhinitis (AR) have increasingly recognized that reactive oxygen species (ROS) are not simply byproducts of oxidative metabolism but function as modulators of the type 2 inflammatory network during the pathogenesis of this disease. This narrative review summarizes the role of ROS in the pathophysiology of AR by analyzing studies that examined markers of systemic oxidative stress, dysfunction of the epithelial barrier, ROS derived from immune cells, mitochondrial redox signaling, and inflammasome-related pathways. Our structured search of the literature reviewed five major databases (PubMed, Scopus, EMBASE, Cochrane Library, and Google Scholar) and identified 17 eligible studies published between 2000 and 2026. Clinical studies suggest that patients with AR exhibit altered systemic redox homeostasis, including thiol-disulfide imbalance and increased lipid peroxidation. However, these findings are primarily from measurements of markers in peripheral blood, not nasal mucosa. Experimental studies consistently demonstrated that allergen exposure increased the levels of ROS in nasal epithelial and immune cells, disrupted the epithelial barrier, downregulated tight junction proteins, and activated inflammatory signaling pathways. Although direct nasal tissue data remain limited, evidence extrapolated from peripheral blood and bronchial challenge models suggests that eosinophils and neutrophils contribute to the generation of ROS during the late phase of the allergic response, thereby potentially amplifying and sustaining airway inflammation. There is also evidence that mitochondrial ROS and DUOX-dependent signaling contribute to epithelial dysfunction, including the release of damage-associated molecular patterns and activation of inflammasome pathways. In parallel, antioxidant defense mechanisms, such as the KEAP1/NRF2 axis and mitophagy-related pathways, appear to modulate disease severity by maintaining redox homeostasis. Experimental strategies such as ROS scavengers and oxidative stress-responsive drug delivery systems have shown early proof-of-concept potential in preclinical and pilot studies, but rigorous and large-scale clinical support is strictly required before any clinical application can be considered. Overall, current evidence indicates that ROS function in AR as context-dependent redox mediators rather than as primary causes. The biological effects of ROS appear to depend on site of synthesis, subcellular localization, and the balance between oxidant generation and antioxidant defenses. Further studies that directly assess the dynamics of nasal mucosal ROS and well-designed clinical trials are needed to clarify the translational relevance of these studies and the therapeutic potential of different treatments for AR.