McDonald Fiona B, Williams Robert, Sheehan David, O'Halloran Ken D
School of Medicine and Medical Science, Health Sciences Centre, University College Dublin, Dublin, Ireland.
Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
Exp Physiol. 2015 Aug;100(8):947-66. doi: 10.1113/EP085003. Epub 2015 Jul 14.
What is the central question of this study? Chronic intermittent hypoxia (CIH) is a dominant feature of respiratory control disorders, which are common. We sought to examine the effects of exposure to CIH during neonatal development on respiratory muscle form and function in male and female rats. What is the main finding and its importance? Exposure to CIH during neonatal development caused sternohyoid muscle weakness in both sexes; an effect that persisted into young adult life upon return to normoxia. Upper airway dilator muscle dysfunction in vivo could predispose to airway collapse, leading to impaired respiratory homeostasis. Chronic intermittent hypoxia (CIH) is a feature of sleep-disordered breathing, which is very common. Exposure to CIH is associated with aberrant plasticity in the respiratory control system including the final effector organs, the striated muscles of breathing. We reasoned that developmental age and sex are key factors determining the functional response of respiratory muscle to CIH. We tested the hypothesis that exposure to CIH causes persistent impairment of sternohyoid muscle function due to oxidative stress and that males are more susceptible to CIH-induced muscle impairment than females. Wistar rat litters (with respective dams) were exposed to intermittent hypoxia for 12 cycles per hour, 8 h per day for 3 weeks from the first day of life [postnatal day (P) 0]. Sham experiments were run in parallel. Half of each litter was studied on P22; the other half was returned to normoxia and studied on P42. Functional properties of the sternohyoid muscle were determined ex vivo. Exposure to CIH significantly decreased sternohyoid muscle force in both sexes; an effect that persisted into young adult life. Chronic intermittent hypoxia had no effect on sternohyoid muscle endurance. Chronic intermittent hypoxia did not affect sternohyoid myosin fibre type, succinate dehydrogenase or glycerol-3-phosphate dehydrogenase activities, or protein free thiol and carbonyl content. Muscles exposed to CIH had smaller cross-sectional areas, consistent with the observation of muscle weakness. In human infants with disordered breathing, CIH-induced upper airway dilator muscle weakness could increase the propensity for airway narrowing or collapse, which could serve to perpetuate impaired respiratory homeostasis.
本研究的核心问题是什么？慢性间歇性缺氧（CIH）是常见的呼吸控制障碍的一个主要特征。我们试图研究新生发育期间暴露于CIH对雄性和雌性大鼠呼吸肌形态和功能的影响。主要发现及其重要性是什么？新生发育期间暴露于CIH导致两性的胸骨舌骨肌无力；这种影响在恢复正常氧水平后持续到年轻成年期。体内上呼吸道扩张肌功能障碍可能易导致气道塌陷，从而导致呼吸稳态受损。慢性间歇性缺氧（CIH）是睡眠呼吸障碍的一个特征，睡眠呼吸障碍非常常见。暴露于CIH与呼吸控制系统包括最终效应器官（呼吸横纹肌）的异常可塑性有关。我们推断发育年龄和性别是决定呼吸肌对CIH功能反应的关键因素。我们检验了以下假设：暴露于CIH由于氧化应激导致胸骨舌骨肌功能持续受损，并且雄性比雌性更易受CIH诱导的肌肉损伤影响。从出生第一天（出生后第0天）起，将Wistar大鼠幼崽（及其各自的母鼠）每天8小时、每周3周暴露于每小时12个周期的间歇性缺氧环境中。同时进行假手术实验。每窝幼崽的一半在出生后第22天进行研究；另一半恢复正常氧水平并在出生后第42天进行研究。在体外测定胸骨舌骨肌的功能特性。暴露于CIH显著降低了两性的胸骨舌骨肌力；这种影响持续到年轻成年期。慢性间歇性缺氧对胸骨舌骨肌耐力没有影响。慢性间歇性缺氧不影响胸骨舌骨肌肌球蛋白纤维类型、琥珀酸脱氢酶或甘油-3-磷酸脱氢酶活性，或蛋白质游离巯基和羰基含量。暴露于CIH的肌肉横截面积较小，这与肌肉无力的观察结果一致。在呼吸障碍的人类婴儿中，CIH诱导的上呼吸道扩张肌无力可能会增加气道变窄或塌陷的倾向，这可能会使受损的呼吸稳态持续存在。
