Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Appl Physiol (1985). 2013 Aug 15;115(4):474-82. doi: 10.1152/japplphysiol.00330.2013. Epub 2013 May 30.
Obesity is a primary risk factor for the development of obstructive sleep apnea in humans, but the impact of obesity on central sleep apnea is less clear. Given the comorbidities associated with obesity in humans, we developed techniques for long-term recording of diaphragmatic EMG activity and polysomnography in obese mice to assess breathing patterns during sleep and to determine the effect of obesity on apnea generation. We hypothesized that genetically obese ob/ob mice would exhibit less variability in breathing across the 24-h circadian cycle, be more prone to central apneas, and be more likely to exhibit patterns of increased diaphragm muscle activity consistent with obstructive apneas compared with lean mice. Unexpectedly, we found that obese mice exhibited a greater circadian impact on respiratory rate and diaphragmatic burst amplitude than lean mice, particularly during rapid eye movement (REM) sleep. Central apneas were more common in REM sleep (42 ± 17 h(-1)) than non-REM (NREM) sleep (14 ± 5 h(-1)) in obese mice (P < 0.05), but rates were not different between lean and obese mice in either sleep state. Even after experimentally enhancing central apnea generation by acute withdrawal of hypoxic chemoreceptor activation during sleep, central apnea rates remained comparable between lean and obese mice. Last, we were unable to detect patterns of diaphragmatic burst activity suggestive of obstructive apnea events in obese mice. In summary, obesity does not predispose mice to increased occurrence of central or obstructive apneas during sleep, but does lead to a more pronounced circadian variability in respiration.
肥胖是人类发生阻塞性睡眠呼吸暂停的主要危险因素，但肥胖对中枢性睡眠呼吸暂停的影响尚不清楚。鉴于肥胖与人类的多种合并症相关，我们开发了长期记录肥胖小鼠膈肌肌电图活动和多导睡眠图的技术，以评估睡眠期间的呼吸模式，并确定肥胖对呼吸暂停发生的影响。我们假设肥胖的 ob/ob 小鼠在 24 小时昼夜节律周期中呼吸的变化性更小，更容易发生中枢性呼吸暂停，并且更有可能表现出与阻塞性呼吸暂停一致的膈肌肌肉活动增加模式，与瘦小鼠相比。出乎意料的是，我们发现肥胖小鼠的呼吸频率和膈肌爆发幅度的昼夜节律影响大于瘦小鼠，尤其是在快速眼动 (REM) 睡眠期间。肥胖小鼠的 REM 睡眠（42 ± 17 次/小时）比非快速眼动 (NREM) 睡眠（14 ± 5 次/小时）中更常见中枢性呼吸暂停（P < 0.05），但在 REM 和 NREM 睡眠中，瘦小鼠和肥胖小鼠的呼吸暂停发生率没有差异。即使在睡眠期间急性抑制缺氧感受器激活以增强中枢性呼吸暂停的发生后，瘦小鼠和肥胖小鼠的中枢性呼吸暂停发生率仍然相似。最后，我们未能检测到肥胖小鼠膈肌爆发活动模式提示阻塞性呼吸暂停事件。总之，肥胖不会导致小鼠在睡眠中发生中枢性或阻塞性呼吸暂停的发生率增加，但会导致呼吸的昼夜节律变化更加明显。
