Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland.
Exp Physiol. 2022 Aug;107(8):946-964. doi: 10.1113/EP090536. Epub 2022 Jul 11.
What is the central question of this study? Exposure to chronic intermittent hypoxia (CIH) evokes redox changes, culminating in impaired upper airway muscle function: what is the specific source of CIH-induced reactive oxygen species? What is the main finding and its importance? Profound sternohyoid muscle dysfunction following exposure to CIH was entirely prevented by apocynin co-treatment or NADPH oxidase 2 (NOX2) deletion. The results have implications for human obstructive sleep apnoea syndrome and point to antioxidant intervention, potentially targeting NOX2 blockade, as a therapeutic strategy.
Exposure to chronic intermittent hypoxia (CIH) evokes redox changes, culminating in impaired upper airway muscle function. We sought to determine if NADPH oxidase 2 (NOX2)-derived reactive oxygen species underpin CIH-induced maladaptive changes in upper airway (sternohyoid) muscle performance. Adult male mice (C57BL/6J) were assigned to one of three groups: normoxic controls (sham); CIH-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) given in the drinking water throughout exposure to CIH. In addition, we studied sham and CIH-exposed NOX2-null mice (B6.129S-CybbTM ). Profound sternohyoid muscle dysfunction following exposure to CIH was entirely prevented by apocynin co-treatment or NOX2 deletion. Exposure to CIH increased sternohyoid muscle NOX enzyme activity, with no alteration to the gene or protein expression of NOX subunits. There was no evidence of overt oxidative stress, muscle regeneration, inflammation or atrophy following exposure to CIH. We suggest that NOX-dependent CIH-induced upper airway muscle weakness increases vulnerability to upper airway obstruction. Our results have implications for human obstructive sleep apnoea syndrome and point to antioxidant intervention, potentially targeting NOX2 blockade, as a therapeutic strategy.
本研究的核心问题是什么？慢性间歇性低氧（CIH）暴露会引发氧化还原变化，最终导致上气道肌肉功能受损：CIH 诱导的活性氧的具体来源是什么？主要发现及其重要性是什么？在 CIH 暴露后，使用 apocynin 共处理或 NADPH 氧化酶 2（NOX2）缺失可完全预防胸骨舌骨肌功能障碍。结果提示与人类阻塞性睡眠呼吸暂停综合征有关，并指出抗氧化剂干预，可能靶向 NOX2 阻断，作为一种治疗策略。
CIH 暴露会引发氧化还原变化，最终导致上气道肌肉功能受损。我们试图确定 NADPH 氧化酶 2（NOX2）衍生的活性氧是否是 CIH 引起的上气道（胸骨舌骨肌）肌肉性能适应性变化的基础。将成年雄性小鼠（C57BL/6J）分为三组：常氧对照组（假手术）；CIH 暴露组（CIH，12 个/小时，8 小时/天，共 14 天）；以及在 CIH 暴露期间通过饮用水给予 apocynin（NOX2 抑制剂，2 mM）。此外，我们还研究了 sham 和 CIH 暴露的 NOX2 缺失小鼠（B6.129S-CybbTM）。在 CIH 暴露后，apocynin 共处理或 NOX2 缺失完全预防了胸骨舌骨肌功能障碍。CIH 暴露增加了胸骨舌骨肌的 NOX 酶活性，而 NOX 亚基的基因或蛋白表达没有改变。CIH 暴露后没有明显的氧化应激、肌肉再生、炎症或萎缩的证据。我们认为，NOX 依赖性 CIH 诱导的上气道肌肉无力增加了上气道阻塞的易感性。我们的研究结果提示与人类阻塞性睡眠呼吸暂停综合征有关，并指出抗氧化剂干预，可能靶向 NOX2 阻断，作为一种治疗策略。
