Pulmonology Department, Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Barcelona, Spain.
Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
J Cell Physiol. 2021 Apr;236(4):3083-3098. doi: 10.1002/jcp.30073. Epub 2020 Sep 28.
Sarcopenia is a major comorbidity in chronic obstructive pulmonary (COPD). Whether deficient muscle repair mechanisms and regeneration exist in the vastus lateralis (VL) of sarcopenic COPD remains debatable. In the VL of control subjects and severe COPD patients with/without sarcopenia, satellite cells (SCs) were identified (immunofluorescence, specific antibodies, anti-Pax-7, and anti-Myf-5): activated (Pax-7+/Myf-5+), quiescent/regenerative potential (Pax-7+/Myf-5-), and total SCs, nuclear activation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling [TUNEL]), and muscle fiber type (morphometry and slow- and fast-twitch, and hybrid fibers), muscle damage (hematoxylin-eosin staining), muscle regeneration markers (Pax-7, Myf-5, myogenin, and MyoD), and myostatin levels were identified. Compared to controls, in VL of sarcopenic COPD patients, myostatin content, activated SCs, hybrid fiber proportions, TUNEL-positive cells, internal nuclei, and muscle damage significantly increased, while quadriceps muscle strength, numbers of Pax-7+/Myf-5- and slow- and fast-twitch, and hybrid myofiber areas decreased. In the VL of sarcopenic and nonsarcopenic patients, TUNEL-positive cells were greater, whereas muscle regeneration marker expression was lower than in controls. In VL of severe COPD patients regardless of the sarcopenia level, the muscle regeneration process is triggered as identified by SC activation and increased internal nuclei. Nonetheless, a lower regenerative potential along with significant alterations in muscle phenotype and damage, and increased myostatin were prominently seen in sarcopenic COPD.
肌肉减少症是慢性阻塞性肺疾病（COPD）的主要合并症。在肌肉减少症 COPD 患者的股外侧肌（VL）中是否存在肌肉修复机制缺陷和再生仍存在争议。在对照受试者和严重 COPD 患者（有/无肌肉减少症）的 VL 中，鉴定了卫星细胞（SCs）（免疫荧光，特异性抗体，抗 Pax-7 和抗 Myf-5）：激活（Pax-7+/Myf-5+），静止/再生潜能（Pax-7+/Myf-5-）和总 SCs，核激活（末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记 [TUNEL]）以及肌纤维类型（形态测量和慢肌和快肌，以及混合纤维），肌肉损伤（苏木精-伊红染色），肌肉再生标志物（Pax-7、Myf-5、myogenin 和 MyoD）和肌肉生长抑制素水平。与对照组相比，在肌肉减少症 COPD 患者的 VL 中，肌肉生长抑制素含量、激活的 SCs、混合纤维比例、TUNEL 阳性细胞、内核和肌肉损伤显着增加，而股四头肌力量、Pax-7+/Myf-5-和慢肌和快肌以及混合肌纤维区域减少。在肌肉减少症和非肌肉减少症患者的 VL 中，TUNEL 阳性细胞更多，而肌肉再生标志物的表达低于对照组。在严重 COPD 患者的 VL 中，无论肌肉减少症的严重程度如何，都可以通过 SC 激活和增加的内核来识别肌肉再生过程。尽管如此，在肌肉减少症 COPD 中，明显可见较低的再生潜能以及肌肉表型和损伤的显着改变，以及肌肉生长抑制素的增加。
