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β2肾上腺素能受体激动剂特布他林可恢复大鼠在严重缺氧期间咽扩张肌力量的下降。

The β2 -adrenoceptor agonist terbutaline recovers rat pharyngeal dilator muscle force decline during severe hypoxia.

作者信息

McDonald F B, Skelly J R, O'Halloran K D

机构信息

School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.

出版信息

Oral Dis. 2015 Jan;21(1):e121-7. doi: 10.1111/odi.12247. Epub 2014 Apr 30.

DOI:10.1111/odi.12247
PMID:24725067
Abstract

RATIONALE

Obstructive sleep apnoea syndrome (OSAS) is a debilitating condition characterized by recurrent occlusions of the pharyngeal airway during sleep accompanied by arterial hypoxaemia. Upper airway muscle dysfunction is implicated in the pathophysiology of OSAS. Pharmacological agents that improve muscle contractile and endurance properties may have therapeutic value.

AIM

We tested the hypothesis that the β(2) -adrenoceptor agonist terbutaline improves rat sternohyoid muscle performance especially during hypoxic stress.

METHODS

Isometric contractile and endurance properties were examined ex vivo in Krebs solution at 35°C. Muscles were incubated in tissue baths under hyperoxic (95% O(2) /5% CO(2)) conditions in the absence (control) or presence of the β(2) -adrenoceptor agonist terbutaline (1 μM). In additional experiments under hypoxic (95% N(2) /5% CO(2)) conditions, the effects of terbutaline were examined in the presence of the β-adrenoceptor antagonist propranolol (1 μM).

RESULTS

Hypoxia significantly impaired sternohyoid force production. Terbutaline completely recovered hypoxic depression of force, an effect that was blocked by co-application with propranolol.

CONCLUSION

The β(2) -adrenoceptor agonist terbutaline completely recovers hypoxic depression of upper airway muscle force. β(2) -adrenoceptor agonists warrant investigation in animal models of OSAS reporting upper airway and diaphragm muscle dysfunction.

摘要

理论依据

阻塞性睡眠呼吸暂停综合征(OSAS)是一种使人衰弱的病症,其特征为睡眠期间咽部气道反复阻塞并伴有动脉血氧不足。上呼吸道肌肉功能障碍与OSAS的病理生理学有关。改善肌肉收缩和耐力特性的药物可能具有治疗价值。

目的

我们检验了β₂肾上腺素能受体激动剂特布他林可改善大鼠胸骨舌骨肌性能,尤其是在低氧应激期间这一假设。

方法

在35℃的 Krebs 溶液中对离体肌肉的等长收缩和耐力特性进行检测。肌肉在组织浴中于高氧(95% O₂/5% CO₂)条件下孵育,分别在不存在(对照)或存在β₂肾上腺素能受体激动剂特布他林(1 μM)的情况下进行。在低氧(95% N₂/5% CO₂)条件下的额外实验中,在存在β肾上腺素能受体拮抗剂普萘洛尔(1 μM)的情况下检测特布他林的作用。

结果

低氧显著损害胸骨舌骨肌的力量产生。特布他林完全恢复了低氧导致的力量降低,与普萘洛尔共同应用可阻断这一效应。

结论

β₂肾上腺素能受体激动剂特布他林完全恢复了上呼吸道肌肉力量的低氧性降低。β₂肾上腺素能受体激动剂值得在报告上呼吸道和膈肌功能障碍的OSAS动物模型中进行研究。

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Front Physiol. 2016 Jul 12;7:276. doi: 10.3389/fphys.2016.00276. eCollection 2016.
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Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during Adulthood.早年暴露于慢性间歇性低氧环境会使成年大鼠胸骨舌骨肌对低氧诱导的无力更加易感。
Front Physiol. 2016 Mar 4;7:69. doi: 10.3389/fphys.2016.00069. eCollection 2016.
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Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction in mouse sternohyoid muscle.
慢性持续性缺氧诱导的氧化还原重塑导致小鼠胸骨舌骨肌收缩功能障碍。
Front Physiol. 2015 Apr 20;6:122. doi: 10.3389/fphys.2015.00122. eCollection 2015.