Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice
Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice
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DOI：
10.1249/mss.0000000000001195
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发表时间：
2017-05-01
期刊：
影响因子：
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通讯作者：
Bronstad, Eivind
中科院分区：
文献类型：
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作者：
Bowen, T. Scott;Aakeroy, Lars;Bronstad, Eivind
目的：吸烟是慢性阻塞性肺疾病和肺气肿的主要危险因素。然而，关于肺损伤前烟雾暴露的肺外效应的证据目前仍不清楚，非药物治疗如运动训练的数据也不清楚。研究方法：将小鼠分为对照组（n = 10）、吸烟组（n = 10）和吸烟+高强度间歇跑台运动组（n = 11），每组10只。随后测量运动能力（峰值摄氧量）和肺破坏（组织学），同时评估心脏、外周内皮（主动脉）、呼吸（膈肌）和肢体（趾长伸肌和比目鱼肌）肌肉的体内和体外功能、原位线粒体呼吸和分子改变。结果：吸烟组体重下降26%（P < 0.05），无明显气道损害（P > 0.05）。吸烟可使运动能力降低15%，右心室功能障碍降低20%，内皮功能障碍降低20%，膈肌无力降低15%（均P < 0.05），但运动训练可减轻或逆转这些损害（P < 0.05）。与对照组相比，吸烟小鼠肢体肌肉和线粒体功能（心肌和骨骼肌纤维）正常，但膈肌氧化应激和蛋白质降解指标分别增加111%和65%（P < 0.05），但运动训练可减弱这些指标（P < 0.05）。结论：长期吸烟会降低运动能力，并伴随心脏、外周内皮和呼吸肌的功能损害，这些损害先于明显的肺气肿的发展。然而，高强度运动训练能够逆转这些吸烟引起的肺外损伤。
Purpose: Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training. Methods: Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorumlongus and soleus) skeletalmuscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations. Results: Smoking reduced body weight by 26% (P < 0.05) without overt airway destruction (P > 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by similar to 20%, endothelial dysfunction by similar to 20%, and diaphragm muscle weakness by similar to 15% (all P < 0.05), but these were either attenuated or reversed by exercise training (P < 0.05). Compared with controls, smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradationwere increased by 111% and 65%, respectively (P < 0.05), but these were attenuated by exercise training (P < 0.05). Conclusions: Prolonged cigarette smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, highintensity exercise training was able to reverse these smoke-induced extrapulmonary impairments.