{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:56:54Z","timestamp":1789390614035,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82474196"],"award-info":[{"award-number":["82474196"]}]},{"name":"National Natural Science Foundation of China","award":["ZYYCXTD-D-202207"],"award-info":[{"award-number":["ZYYCXTD-D-202207"]}]},{"name":"Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine","award":["82474196"],"award-info":[{"award-number":["82474196"]}]},{"name":"Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine","award":["ZYYCXTD-D-202207"],"award-info":[{"award-number":["ZYYCXTD-D-202207"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-altitude environments pose significant risks for insomnia development, which severely compromises both physiological health and occupational performance. To elucidate the mechanisms underlying altitude-induced sleep disruption and establish a validated animal model for therapeutic intervention development, we exposed Sprague-Dawley rats to hypobaric hypoxia (5500 m altitude equivalent: 308 mmHg, 20.37% O2, PiO2 8.0 kPa) for 7 days. We employed continuous wireless telemetry to monitor EEG\/EMG signals, with concurrent analysis of physiological parameters, blood biochemistry, histopathology, transcriptomics, and protein expression. Quantitative analyses demonstrated decreased caloric intake, transient body mass reduction, and immune-metabolic disturbances. While total sleep duration showed no significant variation, sleep architecture displayed elevated wakefulness periods, reduced active wakefulness, a decreasing trend of slow-wave sleep (SWS), and increased paradoxical sleep (PS) accompanied by attenuated circadian oscillations. The duration of SWS episodes was significantly shortened, indicating a sleep homeostasis imbalance that peaked on day 3. Biochemical profiling revealed reduced levels of antioxidant enzymes, elevated pro-inflammatory cytokines, and hypothalamic\u2013pituitary\u2013adrenal axis activation. Transcriptomic analyses identified the critical involvement of serotonergic\/glutamatergic synaptic regulation, lipid metabolism, IL-17 signaling, and cortisol synthesis pathways. Western blot analyses confirmed OX2R upregulation, 5-HT1AR downregulation, and circadian gene dysregulation. Our findings demonstrate that hypobaric hypoxia induces sleep disruption via coordinated mechanisms involving oxidative stress, inflammatory activation, HPA axis hyperactivity, neurotransmitter imbalance, and circadian clock dysfunction, providing a robust preclinical model for mechanistic exploration and therapeutic target identification.<\/jats:p>","DOI":"10.3390\/ijms26114998","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T10:24:45Z","timestamp":1747909485000},"page":"4998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Effects and Mechanisms of Continuous 7-Day Hypobaric Hypoxia Exposure on Sleep Architecture in Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Fang","family":"Li","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-3694","authenticated-orcid":false,"given":"Xianxie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anping","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianke","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xitai","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengrong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengchun","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1089\/ham.2022.0136","article-title":"The Effect of High-Altitude Hypoxia on Neuropsychiatric Functions","volume":"25","author":"Liu","year":"2024","journal-title":"High Alt. 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