UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
J Histochem Cytochem. 2013 Jul;61(7):487-99. doi: 10.1369/0022155413490947. Epub 2013 May 2.
Respiratory muscle remodeling occurs in human sleep apnea--a common respiratory disorder characterized by chronic intermittent hypoxia (CIH) due to recurrent apnea during sleep. We sought to determine if CIH causes remodeling in rat sternohyoid (upper airway dilator) and diaphragm muscles. Adult male Wistar rats were exposed to CIH (n=8), consisting of 90 sec of hypoxia (5% at the nadir; SaO₂ ~80%)/90 sec of normoxia, 8 hr per day, for 7 consecutive days. Sham animals (n=8) were exposed to alternating air/air cycles in parallel. The effect of CIH on myosin heavy-chain (MHC) isoform (1, 2a, 2x, 2b) distribution, sarcoplasmic reticulum calcium ATPase (SERCA) isoform distribution, succinate dehydrogenase activity, glycerol phosphate dehydrogenase activity, and Na⁺/K⁺ ATPase pump content was determined. Sternohyoid muscle structure was unaffected by CIH treatment. CIH did not alter oxidative/glycolytic capacity or the Na⁺/K⁺-ATPase pump content of the diaphragm. CIH significantly increased the areal density of MHC 2b fibers in the rat diaphragm, and this was associated with a shift in SERCA proteins from SERCA2 to SERCA1. We conclude that CIH causes a slow-to-fast fiber transition in the rat diaphragm after just 7 days of treatment. Respiratory muscle functional remodeling may drive aberrant functional plasticity such as decreased muscle endurance, which is a feature of human sleep apnea.
在人类睡眠呼吸暂停中会发生呼吸肌重塑——这是一种常见的呼吸系统疾病，其特征是慢性间歇性低氧（CIH），由于睡眠期间反复出现呼吸暂停。我们试图确定 CIH 是否会导致大鼠胸骨舌骨（上呼吸道扩张肌）和膈肌发生重塑。成年雄性 Wistar 大鼠接受 CIH（n=8），包括 90 秒缺氧（最低点为 5%；SaO₂~80%）/90 秒正常氧，每天 8 小时，连续 7 天。假手术动物（n=8）在平行的交替空气/空气循环中暴露。CIH 对肌球蛋白重链（MHC）同工型（1、2a、2x、2b）分布、肌浆网钙 ATP 酶（SERCA）同工型分布、琥珀酸脱氢酶活性、甘油磷酸脱氢酶活性和 Na⁺/K⁺ATP 酶泵含量的影响。CIH 处理对胸骨舌骨肌结构没有影响。CIH 没有改变膈肌的氧化/糖酵解能力或 Na⁺/K⁺-ATP 酶泵含量。CIH 显著增加了大鼠膈肌中 MHC 2b 纤维的面积密度，这与 SERCA 蛋白从 SERCA2 向 SERCA1 的转移有关。我们得出结论，仅仅 7 天的治疗后，CIH 会导致大鼠膈肌中的慢肌向快肌纤维转变。呼吸肌功能重塑可能会导致异常的功能可塑性，例如肌肉耐力降低，这是人类睡眠呼吸暂停的一个特征。
