Division of Pediatric Otolaryngology-Head and Neck Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Laryngoscope. 2024 Feb;134 Suppl 4(Suppl 4):S1-S11. doi: 10.1002/lary.30915. Epub 2023 Aug 4.
Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short- versus long-term exposure to intermittent hypoxia (IH) on pro-inflammatory mediators within vulnerable organs impacted by OSA.
Experimental animal study.
A total of 8-10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short-term) or 6 weeks (long-term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro-inflammatory mediators from peripheral tissues.
We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short-term exposure to IH. Although there were tissue-specific alterations in the gene expression of pro-inflammatory mediators, with down-regulation in the lung and up-regulation in the heart, we also observed reduced protein levels of pro-inflammatory mediators in the serum, lung, and heart following short-term exposure to IH. Long-term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart.
We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs.
NA Laryngoscope, 134:S1-S11, 2024.
阻塞性睡眠呼吸暂停（OSA）的特征是慢性全身炎症；然而，这些病理后果的机制尚不完全清楚。我们的目的是确定短期和长期暴露于间歇性低氧（IH）对受 OSA 影响的脆弱器官中促炎介质的影响。
实验动物研究。
总共 8-10 周龄的 C57BL/6J 小鼠在 12 小时光照、12 小时黑暗周期下，分别暴露于常氧或 IH 条件下 7 天（短期）或 6 周（长期）。暴露后，在 24 小时内收集多个组织。对这些组织进行处理和评估，以确定外周组织中促炎介质的基因表达和蛋白水平。
与其他外周器官相比，短期暴露于 IH 后，心脏、肺和肝脏的免疫反应途径出现整体下降。尽管促炎介质的基因表达存在组织特异性改变，肺下调，心脏上调，但我们也观察到短期暴露于 IH 后血清、肺和心脏中促炎介质的蛋白水平降低。长期暴露于 IH 导致血清、肺和心脏中炎症介质的水平总体增加。
我们在 OSA 小鼠模型中证明了炎症级联的新的、纵向变化。IH 暴露的持续时间导致血液和心肺组织内炎症反应的显著差异。我们的研究结果进一步阐明了炎症反应在脆弱器官中随着疾病的发展如何变化。
无喉镜，134：S1-S11，2024。
