儿童阻塞性睡眠呼吸暂停综合征中的氧化应激：一项叙述性综述

文献信息

中文摘要

儿童阻塞性睡眠呼吸暂停综合征（OSAS）是一种常见的睡眠相关呼吸障碍，日益被认为是一种多系统疾病，而非孤立的上气道疾病。反复发作的上气道阻塞产生间歇性缺氧、复氧和睡眠碎片化，促进活性氧和活性氮的过度产生以及抗氧化防御的破坏。本叙述性综述总结了关于儿童OSAS中氧化应激的机制、生物标志物和临床后果的当前证据。间歇性缺氧激活多种氧化还原敏感通路，包括NADPH氧化酶、缺氧诱导因子-1α、核因子-κB、线粒体功能障碍和内质网应激，从而在氧化应激与全身性炎症之间形成双向关系。儿童研究已证明脂质过氧化产物、谷胱甘肽氧化还原平衡、尿8-羟基-2'-脱氧鸟苷、异前列腺素、NOX2相关标志物和炎症介质发生改变。这些异常与内皮功能障碍以及心血管、神经认知、代谢、肝脏、肾脏和免疫后果相关，其中若干项在有效治疗后可能改善。重要的是，氧化损伤和终末器官损伤的幅度并不始终与呼吸暂停-低通气指数平行，提示缺氧负荷、肥胖、遗传易感性、抗氧化能力和疾病持续时间影响个体生物学脆弱性。尽管若干氧化生物标志物显示出用于疾病表征和治疗监测的潜力，但方法学异质性和缺乏标准化的儿童参考值目前限制了其临床应用。未来将多导睡眠图缺氧负荷指标与氧化、炎症、代谢组学和基因组学生物标志物相结合，可能改善风险分层并促进儿童OSAS的更个性化管理。

英文摘要

Pediatric obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder increasingly recognized as a multisystem disease rather than an isolated disorder of the upper airway. Recurrent episodes of upper airway obstruction generate intermittent hypoxia, reoxygenation, and sleep fragmentation, promoting excessive production of reactive oxygen and nitrogen species and disruption of antioxidant defenses. This narrative review summarizes current evidence regarding the mechanisms, biomarkers, and clinical consequences of oxidative stress in pediatric OSAS. Intermittent hypoxia activates several redox-sensitive pathways, including NADPH oxidases, hypoxia-inducible factor-1α, nuclear factor-κB, mitochondrial dysfunction, and endoplasmic reticulum stress, thereby creating a bidirectional relationship between oxidative stress and systemic inflammation. Pediatric studies have demonstrated alterations in lipid peroxidation products, glutathione redox balance, urinary 8-hydroxy-2'-deoxyguanosine, isoprostanes, NOX2-related markers, and inflammatory mediators. These abnormalities are associated with endothelial dysfunction and cardiovascular, neurocognitive, metabolic, hepatic, renal, and immune consequences, and several may improve following effective treatment. Importantly, the magnitude of oxidative and end-organ injury does not consistently parallel the apnea-hypopnea index, suggesting that hypoxic burden, obesity, genetic susceptibility, antioxidant capacity, and disease duration influence individual biological vulnerability. Although several oxidative biomarkers show potential for disease characterization and treatment monitoring, methodological heterogeneity and the absence of standardized pediatric reference values currently limit their clinical application. Future integration of polysomnographic hypoxic-burden metrics with oxidative, inflammatory, metabolomic, and genomic biomarkers may improve risk stratification and facilitate more personalized management of pediatric OSAS.