阻塞性睡眠呼吸暂停中认知衰退与神经保护的分子驱动因素：一篇叙述性综述

文献信息

中文摘要

背景： 阻塞性睡眠呼吸暂停是一种常见的睡眠障碍，以慢性间歇性缺氧（CIH）、睡眠碎片化和上气道塌陷为特征。除呼吸问题外，OSA显著影响中枢神经系统，增加轻度认知障碍和痴呆的风险。本综述综合了CIH诱导的分子级联反应的双重性质，描述了驱动神经退行的通路，如SUMO化失调、Toll样受体信号传导和炎症小体过度激活（主要在实验和动物CIH模型中得到表征），以及激活内源性神经保护性适应的通路。生理防御机制，如促红细胞生成素上调、向无氧糖酵解的转变以及神经营养因子的激活，可能起到减轻神经元损伤的作用。这些分子反应并非作为独立过程起作用，而是形成神经元损伤与内源性神经保护之间的动态平衡。在此，我们引入“神经保护储备”的概念，作为一个新的、产生假设的框架，用以描述这种针对缺氧应激的内在缓冲能力。理解并在临床上验证这些通路对于开发早期诊断生物标志物和靶向辅助干预措施至关重要，这些措施可补充标准治疗，以防止不可逆的神经认知衰退。

英文摘要

Obstructive sleep apnea is a common sleep disorder characterized by chronic intermittent hypoxia (CIH), sleep fragmentation, and upper-airway collapse. Beyond respiratory issues, OSA significantly impacts the central nervous system, increasing the risk for mild cognitive impairment and dementia. This review synthesizes the dual nature of CIH-induced molecular cascades, describing pathways driving neurodegeneration, such as SUMOylation dysregulation, toll-like receptor signaling, and inflammasome overactivation (largely characterized in experimental and animal CIH models), and those activating endogenous neuroprotective adaptations. Physiological defense mechanisms, such as the upregulation of erythropoietin, shifts toward anaerobic glycolysis, and the activation of neurotrophic factors, may act to mitigate neuronal injury. Rather than acting as independent processes, these molecular responses form a dynamic balance between neuronal injury and endogenous neuroprotection. Here, we introduce the concept of 'neuroprotective reserve' as a novel, hypothesis-generating framework to describe this intrinsic buffering capacity against hypoxic stress. Understanding and clinically validating these pathways is critical for developing early diagnostic biomarkers and targeted adjunctive interventions that complement standard therapy to prevent irreversible neurocognitive decline.