Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland.
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland.
Respir Physiol Neurobiol. 2021 Oct;292:103713. doi: 10.1016/j.resp.2021.103713. Epub 2021 Jun 8.
Reactive oxygen species (ROS) are proposed as mediators of chronic intermittent hypoxia (CIH)-induced respiratory plasticity. We sought to determine if NADPH oxidase 2 (NOX2)-derived ROS underpin CIH-induced maladaptive changes in respiratory control. Adult male mice (C57BL/6 J) were assigned to one of three groups: normoxic controls (sham); chronic intermittent hypoxia-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-Cybb). Whole-body plethysmography was used to measure breathing and metabolic parameters. Ventilation (V̇/V̇CO) during normoxia was unaffected by CIH, but apnoea index was increased, which was prevented by apocynin, but not by NOX2 deletion. The ventilatory response to hypercapnia following exposure to CIH was potentiated in NOX2-null mice. Our results reveal ROS-dependent influences on the control of breathing and point to antioxidant intervention as a potential adjunctive therapeutic strategy in respiratory control disorders.
活性氧（ROS）被认为是慢性间歇性低氧（CIH）引起呼吸适应性变化的介质。我们试图确定 NADPH 氧化酶 2（NOX2）衍生的 ROS 是否是 CIH 引起的呼吸控制适应性变化的基础。成年雄性小鼠（C57BL/6 J）被分为三组：常氧对照组（假处理）；慢性间歇性低氧暴露组（CIH，12 个/小时，每天 8 小时，持续 14 天）；以及在整个 CIH 暴露期间通过饮用水给予烟酰胺腺嘌呤二核苷酸磷酸氧化酶 2（NOX2 抑制剂，2 mM）抑制剂的 CIH 暴露组。此外，我们研究了假处理和 CIH 暴露的 NOX2 基因敲除（B6.129S-Cybb）小鼠。全身 plethysmography 用于测量呼吸和代谢参数。常氧下的通气量（V̇/V̇CO）不受 CIH 影响，但呼吸暂停指数增加，烟酰胺腺嘌呤二核苷酸磷酸氧化酶 2 抑制剂可预防呼吸暂停指数增加，但 NOX2 缺失则不能。NOX2 基因敲除小鼠在 CIH 暴露后对高碳酸血症的通气反应增强。我们的结果揭示了 ROS 对呼吸控制的影响，并指出抗氧化干预可能是呼吸控制障碍的潜在辅助治疗策略。
