Departamento de Fisiopatología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Laboratorio de Exploración Funcional Respiratoria, Centro de Tratamiento Intensivo, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Physiol Rep. 2022 Sep;10(17):e15449. doi: 10.14814/phy2.15449.
Acute respiratory distress syndrome is associated with skeletal muscle compromise, which decreases survival and impairs functional capacity. A comparative analysis of peripheral and respiratory muscles' atrophy and dysfunction in acute lung injury (ALI) has not been performed. We aimed to evaluate diaphragmatic and peripheral muscle mass and contractility in an ALI animal model. ALI was induced in C57BL/6 mice by intratracheal lipopolysaccharides instillation. Muscle mass and in vitro contractility were evaluated at different time points in hindlimb soleus (slow-twitch) and extensor digitorum longus (EDL, fast-twitch), as well as in the main respiratory muscle diaphragm. Myogenic precursor satellite cell-specific transcription factor Pax7 expression was determined by Western blot. Lung injury was associated with atrophy of the three studied muscles, although it was more pronounced and persistent in the diaphragm. Specific contractility was reduced during lung injury in EDL muscle but restored by the time lung injury has resolved. Specific force was not affected in soleus and diaphragm. A persistent increase in Pax7 expression was detected in diaphragm and EDL muscles after induction of ALI, but not in soleus muscle. Different peripheral and respiratory skeletal muscles are distinctly affected during the course of ALI. Each of the studied muscles presented a unique pattern in terms of atrophy development, contractile dysfunction and Pax7 expression.
急性呼吸窘迫综合征与骨骼肌功能障碍有关,后者会降低存活率并损害功能能力。尚未对急性肺损伤(ALI)中外周和呼吸肌萎缩和功能障碍进行比较分析。我们旨在评估 ALI 动物模型中的膈肌和外周肌肉质量和收缩性。通过气管内滴注脂多糖诱导 C57BL/6 小鼠发生 ALI。在不同时间点评估后肢比目鱼肌(慢肌)和伸趾长肌(EDL,快肌)以及主要呼吸肌膈肌的肌肉质量和体外收缩性。通过 Western blot 确定肌原性前体细胞卫星细胞特异性转录因子 Pax7 的表达。肺损伤与三种研究肌肉的萎缩有关,但在膈肌中更为明显和持久。在 EDL 肌肉中,肺损伤期间特定的收缩性降低,但在肺损伤解决时恢复。比目鱼肌和膈肌的比特定力不受影响。在诱导 ALI 后,在膈肌和 EDL 肌肉中检测到 Pax7 表达持续增加,但在比目鱼肌中未检测到。在 ALI 发生过程中,不同的外周和呼吸骨骼肌受到明显影响。所研究的每块肌肉在萎缩发展、收缩功能障碍和 Pax7 表达方面都表现出独特的模式。