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阻塞性睡眠呼吸暂停与血清素能信号通路:发病机制与治疗潜力。

Obstructive Sleep Apnea and Serotoninergic Signalling Pathway: Pathomechanism and Therapeutic Potential.

机构信息

Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland.

出版信息

Int J Mol Sci. 2024 Aug 30;25(17):9427. doi: 10.3390/ijms25179427.

Abstract

Obstructive Sleep Apnea (OSA) is a disorder characterized by repeated upper airway collapse during sleep, leading to apneas and/or hypopneas, with associated symptoms like intermittent hypoxia and sleep fragmentation. One of the agents contributing to OSA occurrence and development seems to be serotonin (5-HT). Currently, the research focuses on establishing and interlinking OSA pathogenesis and the severity of the disease on the molecular neurotransmitter omnipresent in the human body-serotonin, its pathway, products, receptors, drugs affecting the levels of serotonin, or genetic predisposition. The 5-HT system is associated with numerous physiological processes such as digestion, circulation, sleep, respiration, and muscle tone-all of which are considered factors promoting and influencing the course of OSA because of correlations with comorbid conditions. Comorbidities include obesity, physiological and behavioral disorders as well as cardiovascular diseases. Additionally, both serotonin imbalance and OSA are connected with psychiatric comorbidities, such as depression, anxiety, or cognitive dysfunction. Pharmacological agents that target 5-HT receptors have shown varying degrees of efficacy in reducing the Apnea-Hypopnea Index and improving OSA symptoms. The potential role of the 5-HT signaling pathway in modulating OSA provides a promising avenue for new therapeutic interventions that could accompany the primary treatment of OSA-continuous positive airway pressure. Thus, this review aims to elucidate the complex role of 5-HT and its regulatory mechanisms in OSA pathophysiology, evaluating its potential as a therapeutic target. We also summarize the relationship between 5-HT signaling and various physiological functions, as well as its correlations with comorbid conditions.

摘要

阻塞性睡眠呼吸暂停(OSA)是一种以睡眠期间反复发生上气道塌陷为特征的疾病,导致呼吸暂停和/或呼吸不足,并伴有间歇性缺氧和睡眠碎片化等相关症状。导致 OSA 发生和发展的因素之一似乎是血清素(5-HT)。目前,研究的重点是确定 OSA 发病机制与疾病严重程度之间的联系,这种联系涉及到人体内普遍存在的分子神经递质——血清素,以及其途径、产物、受体、影响血清素水平的药物或遗传易感性。5-HT 系统与许多生理过程有关,如消化、循环、睡眠、呼吸和肌肉张力——所有这些都被认为是促进和影响 OSA 进程的因素,因为它们与合并症有关。合并症包括肥胖、生理和行为障碍以及心血管疾病。此外,血清素失衡和 OSA 都与精神合并症有关,如抑郁、焦虑或认知功能障碍。针对 5-HT 受体的药物在降低呼吸暂停-低通气指数和改善 OSA 症状方面显示出不同程度的疗效。5-HT 信号通路在调节 OSA 中的潜在作用为新的治疗干预提供了一个有前途的途径,这些干预可以伴随 OSA 的主要治疗——持续气道正压通气。因此,本综述旨在阐明 5-HT 及其调节机制在 OSA 病理生理学中的复杂作用,评估其作为治疗靶点的潜力。我们还总结了 5-HT 信号与各种生理功能之间的关系,以及与合并症的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d14e/11395478/d36ea5fc6150/ijms-25-09427-g001.jpg

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