PhyMedExp, INSERM, CNRS, Université de Montpellier, Montpellier, France.
PhyMedExp, INSERM, CNRS, CHRU Montpellier, Université de Montpellier, Montpellier, France.
Acta Physiol (Oxf). 2024 Jul;240(7):e14165. doi: 10.1111/apha.14165. Epub 2024 May 15.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and development of emphysema. Among the comorbidities associated with COPD, skeletal muscle dysfunction is known to affect exercise capacity and the survival rate of patients. Pulmonary rehabilitation (PR), via exercise training, is essential for COPD patients. However, the response to PR is most often moderate. An animal model that recapitulates critical features of chronic human disease and provides access to muscle function should therefore be useful to improve PR benefits.
We used a rat model of induced emphysema based on pulmonary instillations of elastase (ELA) and lipopolysaccharides (LPS). We assessed the long-term effects of ELA/LPS and the potential effectiveness of endurance training on the skeletal muscle function. In vivo strength of the animals, and ex vivo contractility, endurance, type 1 fiber proportion, fiber cross-sectional area, and capillarization of both soleus and extensor digitorum longus (EDL) were assessed.
An impaired overall muscle strength with decreased force, reduced capillarization, and atrophy of type 1 fiber of EDL was observed in ELA/LPS rats. Soleus was not affected. Endurance training was able to reduce fatigability, and increase type 1 fiber proportion and capillarization of soleus, and improve force, endurance, and capillarization of EDL in control and ELA/LPS rats.
Our rat model of induced emphysema, which shares some features with the phenotype present in patients with COPD, could represent a suitable model to study skeletal muscle dysfunction and the effects of exercise training on muscle function in patients.
慢性阻塞性肺疾病(COPD)的特征是进行性气流阻塞和肺气肿的发展。在与 COPD 相关的合并症中,骨骼肌功能障碍已知会影响运动能力和患者的生存率。肺康复(PR)通过运动训练对 COPD 患者至关重要。然而,PR 的反应通常是中等的。因此,应该有一种能够重现慢性人类疾病关键特征并能够获得肌肉功能的动物模型,以提高 PR 的益处。
我们使用基于弹性蛋白酶(ELA)和脂多糖(LPS)肺内滴注的大鼠肺气肿模型。我们评估了 ELA/LPS 的长期影响以及耐力训练对骨骼肌功能的潜在有效性。评估了动物的体内力量以及比目鱼肌和伸趾长肌(EDL)的离体收缩性、耐力、I 型纤维比例、纤维横截面积和毛细血管化。
在 ELA/LPS 大鼠中观察到整体肌肉力量受损,表现为力量下降、毛细血管化减少和 EDL 的 I 型纤维萎缩。比目鱼肌不受影响。耐力训练能够降低疲劳性,增加比目鱼肌的 I 型纤维比例和毛细血管化,并改善对照和 ELA/LPS 大鼠的 EDL 的力量、耐力和毛细血管化。
我们的诱导肺气肿大鼠模型与 COPD 患者的表型有一些共同特征,可能代表研究骨骼肌功能障碍和运动训练对患者肌肉功能影响的合适模型。