Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
J Appl Physiol (1985). 2012 May;112(10):1637-43. doi: 10.1152/japplphysiol.01222.2011. Epub 2012 Feb 16.
Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob(-)/ob(-) mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P(N)) to determine the passive expiratory critical pressure (P(CRIT)) and active responses to reductions in P(N), including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the P(N) threshold at which IFL developed, maximum inspiratory airflow (Vi(max)), and genioglossus electromyographic (EMG(GG)) activity. Elevations in body weight were associated with progressive elevations in P(CRIT) (0.1 ± 0.02 cmH(2)O/g), independent of mouse strain. P(CRIT) was also elevated in ob(-)/ob(-) compared with BL6 mice (1.6 ± 0.1 cmH(2)O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P(N) threshold and lower VI(max). Very obese ob(-)/ob(-) mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and P(N) threshold (from -0.8 ± 1.1 to -5.6 ± 0.8 cmH(2)O) and increase in VI(max) (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive P(CRIT) in leptin-treated mice did not differ significantly from that seen in nontreated ob(-)/ob(-) mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.
肥胖与睡眠时上气道 collapsibility 的改变有关。肥胖、瘦素缺乏的小鼠表现出通气控制减弱，这使我们假设：（1）肥胖和瘦素缺乏会导致上气道神经机械功能恶化；（2）瘦素替代治疗会在不减轻体重的情况下急性逆转神经肌肉缺陷。在年龄匹配、麻醉、自主呼吸的 C57BL/6J（BL6）和 ob(-)/ob(-) 小鼠中，我们在鼻压（P(N)）逐渐降低时描述了上气道压力-流量动力学，以确定被动呼气临界压力（P(CRIT)）和主动对 P(N)降低的反应，包括显示吸气流量限制（IFL；频率）的 ramp 的百分比、发生 IFL 的 P(N)阈值、最大吸气流量（Vi(max)）和颏舌肌肌电图（EMG(GG)）活性。体重增加与 P(CRIT)的逐渐升高（0.1 ± 0.02 cmH(2)O/g）相关，与小鼠品系无关。与 BL6 小鼠相比，ob(-)/ob(-) 小鼠的 P(CRIT)也升高（1.6 ± 0.1 cmH(2)O），与体重无关。肥胖和瘦素缺乏都与 IFL 频率和 P(N)阈值显著升高以及 VI(max)降低相关。与未治疗的 ob(-)/ob(-) 小鼠相比，用瘦素治疗的非常肥胖的 ob(-)/ob(-) 小鼠的 IFL 频率（从 63.5 ± 2.9 降至 30.0 ± 8.6%）和 P(N)阈值（从-0.8 ± 1.1 降至-5.6 ± 0.8 cmH(2)O）降低，VI(max)（从 354.1 ± 25.3 增至 659.0 ± 71.8 μl/s）增加。然而，瘦素治疗的小鼠的被动 P(CRIT)与未治疗的 ob(-)/ob(-) 小鼠的差异无统计学意义。这些发现表明，体重和瘦素缺乏导致上气道神经机械控制缺陷，而瘦素急性逆转主动神经肌肉反应缺陷，而不减轻机械负荷。
