Systemic leptin produces a long-lasting increase in respiratory motor output in rats.
Systemic leptin produces a long-lasting increase in respiratory motor output in rats.
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DOI：
10.3389/fphys.2013.00016
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发表时间：
2013
影响因子：
4
通讯作者：
McCrimmon DR
中科院分区：
文献类型：
--
作者：
Chang Z;Ballou E;Jiao W;McKenna KE;Morrison SF;McCrimmon DR
瘦素减少食物摄入并增加能量消耗。将瘦素注射到小鼠或大鼠的中枢神经系统中会增加肺泡通气量，而瘦素信号传导功能障碍与肥胖伴随的通气不足有关。这种反应涉及 CO2 化学敏感性的增加，但尚不清楚当 PCO2 保持恒定时通气是否会增强。我们检查了静脉注射瘦素的效果，以检验以下假设：异氟烷麻醉、机械通气和迷走神经切断的大鼠全身注射瘦素会导致呼吸运动输出持续增加，且与呼气末 PCO2、体温或肺膨胀压（肺和胸壁总体顺应性指标）的变化无关。在呼气末 PCO2、肺顺应性和直肠温度保持恒定的麻醉 Sprague-Dawley 大鼠中，注射一剂瘦素（0.25 mg、0.5 mg/ml，静脉注射），然后在接下来的 1 小时内静脉输注另外 0.25 mg，引起整合膈神经放电的峰值幅度逐渐增加，持续至少 1 小时 超过输液结束时间。增加在 90 分钟时达到峰值，比基线高 58.3 ± 5.7%。随着吸入二氧化碳的增加，膈反应的斜率也相应增加。 120 分钟时动脉压也出现中度持续下降 9 ± 1.3 mmHg，心率没有相关变化。这些数据表明，瘦素通过一种不需要改变动脉 PCO2、体温或通过迷走神经的全身传入反馈的机制，引起呼吸运动输出的持续增加，其持续时间比施用瘦素更持久。这种刺激可能有助于预防与肥胖相关的通气不足。
Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO2 chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO2 is maintained constant. We examined the effects of intravenous leptin to test the hypothesis that systemic leptin administration in isoflurane anesthetized, mechanically ventilated and vagotomized rats would lead to a sustained increase in respiratory motor output that was independent of changes in end-tidal PCO2, body temperature or lung inflation pressure (an indicator of overall lung and chest wall compliance). In anesthetized Sprague-Dawley rats with end-tidal PCO2, lung compliance and rectal temperature maintained constant, injection of a bolus of leptin (0.25 mg, 0.5 mg/ml, i.v.), followed over the next 1 h by the intravenous infusion of an additional 0.25 mg, elicited a progressive increase in the peak amplitude of integrated phrenic nerve discharge lasting at least 1 h beyond the end of the infusion. The increase peaked at 90 min at 58.3 ± 5.7% above baseline. There was an associated increase in the slope of the phrenic response to increasing inspired CO2. There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate. These data indicate that leptin elicits a sustained increase in respiratory motor output that outlasts the administration leptin via a mechanism that does not require alterations in arterial PCO2, body temperature, or systemic afferent feedback via the vagus nerves. This stimulation may help to prevent obesity-related hypoventilation.
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DOI：
10.1164/ajrccm.150.2.8049815
发表时间：
1994-08-01
影响因子：
24.7
作者：
FARKAS, GA;SCHLENKER, EH
通讯作者：
SCHLENKER, EH
影响因子：
10
作者：
Phipps, PR;Starritt, E;Grunstein, RR
通讯作者：
Grunstein, RR
影响因子：
--
作者：
Beltowski, J;Jochem, J;Zwirska-Korczala, K
通讯作者：
Zwirska-Korczala, K
影响因子：
7.7
作者：
Dunbar, JC;Hu, YG;Lu, HQ
通讯作者：
Lu, HQ
影响因子：
--
作者：
Inyushkina, E M;Merkulova, N A;Inyushkin, A N
通讯作者：
Inyushkin, A N