Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec, Canada.
University of Lyon, Université Claude Bernard Lyon 1, CNRS, ENTPE, UMR5023 LEHNA, Villeurbanne, F-69622, France.
Exp Physiol. 2020 Jun;105(6):1025-1034. doi: 10.1113/EP088430. Epub 2020 May 6.
What is the central question of this study? Does progesterone reduce the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory control and oxidative stress in the central nervous system in ovariectomized rats? What is the main finding and its importance? Progesterone does not prevent the elevation of arterial blood pressure in rats exposed to CIH, but normalizes respiratory control, and reduces cerebral oxidative stress. This study draws focus to a potential role of progesterone and the consequences of sleep apnoea in menopausal women.
We tested the hypothesis that progesterone (Prog) reduces the effect of chronic intermittent hypoxia (CIH) on arterial blood pressure, respiratory chemoreflexes and oxidative stress in the central nervous system. Ovariectomized female rats were implanted with osmotic pumps delivering vehicle (Veh) or Prog (4 mg kg day ). Two weeks following the surgery, rats were exposed to room air (Air) or CIH (7 days, 10% O , 10 cycles h , 8 h day ). We studied three groups: Veh-Air, Veh-CIH and Prog-CIH. After the CIH exposures, we measured the mean arterial pressure (MAP; tail cuff) and assessed the frequency of apnoeas at rest and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). The activities of the pro-oxidant enzyme NADPH oxidase (NOX) and antioxidant enzymes superoxide dismutase (SOD; in mitochondrial and cytosolic fractions) and glutathione peroxidase (GPx), as well as the concentration of malondialdehyde (MDA), a marker of lipid peroxidation, were measured in brain cortex and brainstem samples. CIH exposure increased the MAP, the frequency of apnoeas, and the respiratory frequency response to hypoxia and hypercapnia. Prog did not prevent the CIH-induced elevation in MAP, but it reduced the CIH-induced frequency of apnoeas and increased hypoxic and hypercapnic ventilatory responses. In the brain cortex, CIH increased NOX activity, and decreased the cytosolic and mitochondrial SOD activities. These effects were prevented by Prog. NOX activity was increased by CIH in the brainstem, and this was also blocked by Prog. The study draws focus to the links between ovarian hormones and the consequences of sleep apnoea in women.
本研究的核心问题是什么？孕激素是否能降低慢性间歇性低氧（CIH）对去卵巢大鼠动脉血压、呼吸控制和中枢神经系统氧化应激的影响？主要发现及其重要性是什么？孕激素不能预防 CIH 暴露大鼠的动脉血压升高，但能使呼吸控制正常化，并降低大脑氧化应激。这项研究强调了孕激素的潜在作用以及睡眠呼吸暂停对绝经后妇女的影响。
我们检验了以下假设：孕激素（Prog）可降低慢性间歇性低氧（CIH）对去卵巢雌性大鼠动脉血压、呼吸化学感受器和中枢神经系统氧化应激的影响。手术后两周，大鼠接受载体（Veh）或 Prog（4mgkg·day）的渗透泵给药。两组大鼠接受空气（Air）或 CIH（7 天，10%O2，10 个周期h，每天 8h）暴露。我们研究了三组：Veh-Air、Veh-CIH 和 Prog-CIH。CIH 暴露后，我们测量平均动脉压（MAP；尾套法）并评估休息时呼吸暂停的频率以及对低氧和高碳酸血症的通气反应（全身 plethysmography）。在大脑皮质和脑干样本中测量促氧化剂酶 NADPH 氧化酶（NOX）和抗氧化酶超氧化物歧化酶（SOD；线粒体和胞质部分）和谷胱甘肽过氧化物酶（GPx）的活性，以及丙二醛（MDA）的浓度，作为脂质过氧化的标志物。CIH 暴露增加了 MAP、呼吸暂停频率以及对低氧和高碳酸血症的呼吸频率反应。Prog 不能预防 CIH 引起的 MAP 升高，但可降低 CIH 引起的呼吸暂停频率，并增加低氧和高碳酸血症的通气反应。在大脑皮质中，CIH 增加了 NOX 活性，降低了胞质和线粒体 SOD 活性。Prog 可预防这些影响。CIH 在脑干中增加了 NOX 活性，这也被 Prog 阻断。这项研究强调了卵巢激素与女性睡眠呼吸暂停后果之间的联系。
