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小鼠中枢性和阻塞性睡眠呼吸暂停的检测:一种新的手术和记录方案。

Detection of central and obstructive sleep apneas in mice: A new surgical and recording protocol.

作者信息

Matteoli Gabriele, Alvente Sara, Berteotti Chiara, Coraci Dario, Lo Martire Viviana, Lops Martina, Miglioranza Elena, Silvani Alessandro, Volino Emilia, Zoccoli Giovanna, Bastianini Stefano

机构信息

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.

出版信息

PLoS One. 2025 Mar 28;20(3):e0320650. doi: 10.1371/journal.pone.0320650. eCollection 2025.

DOI:10.1371/journal.pone.0320650
PMID:40153464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12048029/
Abstract

Sleep apnea is a common respiratory disorder in humans and consists of recurrent episodes of cessation of breathing or decrease in airflow during sleep. Sleep apnea can be classified as central or obstructive, based on its origin. Central sleep apnea results from an impaired transmission of the signal for inspiration from the brain to inspiratory muscles, while obstructive sleep apnea occurs in the presence of an obstruction of the upper airways during inspiration. This condition leads to repetitive episodes of reduced oxygen and elevated carbon dioxide levels in the bloodstream, which entail both direct and indirect adverse effects on vital organs, especially the brain and heart. Basic research on animal models has been instrumental in advancing the understanding of disease mechanisms and pathophysiology, and in expediting the development of targeted therapies in several medical fields. Among animal models, mice are the mammalian species of choice for functional genomics of integrative functions such as sleep. Mice have long been known to show sleep apneas, but the classification of sleep apneas as central or obstructive in mice is technically challenging due to the small size of these animals. Here we present a method aimed at identifying central and obstructive sleep apneas in mice. This method involves the surgical implantation of electrodes for recording the electroencephalogram and nuchal muscle electromyogram, which are the gold standard to study the wake-sleep cycle, and for recording the diaphragm electromyogram, which allows the detection of diaphragm contraction. The method also includes the simultaneous recording of the above-mentioned biological signals and breathing inside a whole-body plethysmograph and the data analysis allows to score wake-sleep states and to detect sleep apneas and categorize them into central and obstructive events.

摘要

睡眠呼吸暂停是人类常见的呼吸系统疾病,表现为睡眠期间呼吸反复停止或气流减少。根据其起源,睡眠呼吸暂停可分为中枢性或阻塞性。中枢性睡眠呼吸暂停是由于大脑向吸气肌肉传递吸气信号受损所致,而阻塞性睡眠呼吸暂停则发生在吸气时上呼吸道存在阻塞的情况下。这种情况会导致血液中氧气反复减少和二氧化碳水平升高,对重要器官,尤其是大脑和心脏产生直接和间接的不良影响。对动物模型的基础研究有助于推进对疾病机制和病理生理学的理解,并加速多个医学领域靶向治疗的开发。在动物模型中,小鼠是进行睡眠等综合功能功能基因组学研究的首选哺乳动物物种。长期以来人们一直知道小鼠会出现睡眠呼吸暂停,但由于这些动物体型小,在小鼠中将睡眠呼吸暂停分类为中枢性或阻塞性在技术上具有挑战性。在此,我们提出一种旨在识别小鼠中枢性和阻塞性睡眠呼吸暂停的方法。该方法包括手术植入电极以记录脑电图和颈部肌肉肌电图(这是研究觉醒 - 睡眠周期的金标准)以及记录膈肌肌电图(这允许检测膈肌收缩)。该方法还包括在全身体积描记器内同时记录上述生物信号和呼吸,数据分析可对觉醒 - 睡眠状态进行评分,并检测睡眠呼吸暂停并将其分类为中枢性和阻塞性事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/296cc9157ca7/pone.0320650.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/dfb729f953f1/pone.0320650.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/eb770aa3a2ee/pone.0320650.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/296cc9157ca7/pone.0320650.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/dfb729f953f1/pone.0320650.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/eb770aa3a2ee/pone.0320650.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f00/12048029/296cc9157ca7/pone.0320650.g003.jpg

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本文引用的文献

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2
Ageing-related modification of sleep and breathing in orexin-knockout narcoleptic mice.食欲素基因敲除发作性睡病小鼠睡眠与呼吸的衰老相关改变
J Sleep Res. 2025 Apr;34(2):e14287. doi: 10.1111/jsr.14287. Epub 2024 Jul 20.
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The efficacy of intranasal leptin for opioid-induced respiratory depression depends on sex and obesity state.
鼻内注射瘦素对阿片类药物引起的呼吸抑制的疗效取决于性别和肥胖状态。
Front Physiol. 2023 Dec 13;14:1320151. doi: 10.3389/fphys.2023.1320151. eCollection 2023.
4
Leptin signaling in the dorsomedial hypothalamus couples breathing and metabolism in obesity.腹内侧下丘脑的瘦素信号传递将肥胖中的呼吸和代谢联系起来。
Cell Rep. 2023 Dec 26;42(12):113512. doi: 10.1016/j.celrep.2023.113512. Epub 2023 Nov 30.
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How to study sleep apneas in mouse models of human pathology.如何在人类病理的小鼠模型中研究睡眠呼吸暂停。
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The effect of diet-induced obesity on sleep and breathing in female mice.饮食诱导肥胖对雌性小鼠睡眠和呼吸的影响。
Sleep. 2023 Aug 14;46(8). doi: 10.1093/sleep/zsad158.
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The integrated brain network that controls respiration.控制呼吸的整合大脑网络。
Elife. 2023 Mar 8;12:e83654. doi: 10.7554/eLife.83654.
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Expression of a Secretable, Cell-Penetrating CDKL5 Protein Enhances the Efficacy of Gene Therapy for CDKL5 Deficiency Disorder.分泌型、穿膜的 CDKL5 蛋白的表达增强了 CDKL5 缺乏症基因治疗的疗效。
Neurotherapeutics. 2022 Oct;19(6):1886-1904. doi: 10.1007/s13311-022-01295-8. Epub 2022 Sep 15.
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The effect of brain serotonin deficiency on breathing is magnified by age.大脑血清素缺乏对呼吸的影响随着年龄的增长而放大。
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