免疫系统与阻塞性睡眠呼吸暂停之间的交互作用

文献信息

中文摘要

背景： 阻塞性睡眠呼吸暂停（OSA）的特征是睡眠期间反复发生上气道阻塞。其标志性病理生理特征——间歇性低氧（IH）和睡眠片段化（SF）——触发细胞和分子反应，破坏免疫稳态。反复的低氧-复氧促进氧化应激，并激活低氧诱导因子-1α（HIF-1α）、核因子-κB（NF-κB）和NLRP3炎症小体，导致持续性炎症信号、内皮功能障碍以及循环和组织驻留免疫细胞的改变。本综述整合了临床和临床前研究的证据，将OSA与先天免疫、适应性免疫和体液免疫的失调联系起来，并探讨这些免疫改变如何促成OSA相关的全身性并发症。方法：结果：OSA中的先天免疫失调表现为中性粒细胞和单核细胞/巨噬细胞活化、氧化应激增加以及促炎介质升高，包括IL-1β、IL-6、IL-8、TNF-α、CRP和MCP-1。ICAM-1和VCAM-1表达的改变可能进一步促进白细胞募集和内皮功能障碍，维持全身性炎症和终末器官损伤。适应性免疫失调包括CD4+和CD8+ T细胞群改变、Th1/Th17极化、Th17/Treg平衡破坏以及调节性T细胞功能受损。新出现的、但相对有限的证据也提示体液免疫失调。结论：总体而言，IH、SF、氧化应激、炎症和免疫功能障碍之间的相互作用支持这一概念：OSA是一种全身性免疫调节障碍，而不仅仅是上气道疾病。先天免疫、适应性免疫和体液免疫的失调可能促成OSA相关的代谢、心血管和神经认知并发症。明确这些免疫机制可能有助于解释OSA的表型异质性，并识别疾病严重程度和治疗反应的生物标志物。此外，表征OSA特异性免疫特征可能有助于患者分层，并推进基于个体炎症和免疫表型的精准医学方法。

英文摘要

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. Its hallmark pathophysiological features, intermittent hypoxia (IH) and sleep fragmentation (SF), trigger cellular and molecular responses that disrupt immune homeostasis. Recurrent hypoxia-reoxygenation promotes oxidative stress and activates hypoxia-inducible factor-1α (HIF-1α), nuclear factor-κB (NF-κB), and the NLRP3 inflammasome, contributing to sustained inflammatory signaling, endothelial dysfunction, and alterations in circulating and tissue-resident immune cells. This review integrates evidence from clinical and preclinical studies linking OSA to dysregulation of innate, adaptive, and humoral immunity and examines how these immune alterations contribute to OSA-associated systemic morbidity. Innate immune dysregulation in OSA is characterized by activation of neutrophils and monocytes/macrophages, increased oxidative stress, and elevated pro-inflammatory mediators, including IL-1β, IL-6, IL-8, TNF-α, CRP, and MCP-1. Altered expressions of ICAM-1 and VCAM-1 may further promote leukocyte recruitment and endothelial dysfunction, sustaining systemic inflammation and end-organ injury. Adaptive immune dysregulation includes alterations in CD4+ and CD8+ T-cell populations, Th1/Th17 polarization, disruption of the Th17/Treg balance, and impaired regulatory T-cell function. Emerging, although comparatively limited, evidence also implicates humoral immune dysregulation. Collectively, the interactions among IH, SF, oxidative stress, inflammation, and immune dysfunction support the concept that OSA is a systemic immune-modulating disorder rather than solely an upper airway disorder. Dysregulation of innate, adaptive, and humoral immunity may contribute to OSA-associated metabolic, cardiovascular, and neurocognitive complications. Defining these immune mechanisms may help explain OSA phenotypic heterogeneity and identify biomarkers of disease severity and therapeutic response. Furthermore, characterization of OSA-specific immune signatures may facilitate patient stratification and advance precision-medicine approaches based on individual inflammatory and immunological phenotypes.