Zhao Ying, Zhang Ying, Song Rui, He Ying, Yao Liqing
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, China.
Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, China.
Pathol Res Pract. 2025 Jun;270:155982. doi: 10.1016/j.prp.2025.155982. Epub 2025 Apr 17.
Heart failure (HF) is a structural or functional abnormality of the heart, often accompanied by skeletal muscle atrophy and other complications. Exercise plays an important role in preventing muscle atrophy. However, the underlying molecular mechanisms related to skeletal muscle atrophy in HF still remain poorly understood. In this study, we constructed an HF rat model by abdominal aortic coarctation (AAC) and a C2C12 muscle atrophy cell model induced by angiotensin II (Ang II). The relevant protein expressions were analyzed using western blotting. The damage of myocardial tissue, gastrocnemius tissue and cells were assessed through echocardiography, ELISA, HE staining, and immunofluorescence staining. Findings from this study indicated that moderate exercise has beneficial effects on pathological damage in the myocardial and gastrocnemius tissues of rats, resulting in a reduction of NT-proBNP levels in the blood. Furthermore, it was observed that the expression levels of MAFbx and MuRF1 were downregulated, while MHC and MyoD expressions were elevated, and the expression of endoplasmic reticulum stress (ERS)-related proteins GRP78, p-eIF2α, p-IRE1α, p-PERK, CHOP, ATF6 was inhibited, and finally alleviated HF-induced skeletal muscle atrophy. The mechanism involves moderate exercise working to alleviate ERS by inhibiting the MAPK/SOCS3 signaling pathway, thus alleviating skeletal muscle atrophy induced by HF. Our study elucidates the positive role of moderate exercise in HF-induced skeletal muscle atrophy, reveals its potential molecular mechanism, and provides a new scientific basis for the comprehensive treatment of skeletal muscle atrophy in HF.
心力衰竭（HF）是一种心脏结构或功能异常，常伴有骨骼肌萎缩等并发症。运动在预防肌肉萎缩方面发挥着重要作用。然而，与HF中骨骼肌萎缩相关的潜在分子机制仍知之甚少。在本研究中，我们通过腹主动脉缩窄（AAC）构建了HF大鼠模型，并通过血管紧张素II（Ang II）诱导建立了C2C12肌肉萎缩细胞模型。使用蛋白质免疫印迹法分析相关蛋白表达。通过超声心动图、酶联免疫吸附测定（ELISA）、苏木精-伊红（HE）染色和免疫荧光染色评估心肌组织、腓肠肌组织及细胞的损伤情况。本研究结果表明，适度运动对大鼠心肌和腓肠肌组织的病理损伤具有有益作用，导致血液中N末端脑钠肽前体（NT-proBNP）水平降低。此外，观察到肌肉萎缩相关因子1（MAFbx）和肌肉特异性泛素连接酶1（MuRF1）的表达水平下调，而肌球蛋白重链（MHC）和肌源性决定因子（MyoD）的表达升高，并且内质网应激（ERS）相关蛋白葡萄糖调节蛋白78（GRP78）、磷酸化真核细胞起始因子2α（p-eIF2α）、磷酸化肌醇需求酶1α（p-IRE1α）、磷酸化蛋白激酶R样内质网激酶（p-PERK）、 Chop蛋白（CHOP）、活化转录因子6（ATF6）的表达受到抑制，最终减轻了HF诱导的骨骼肌萎缩。其机制涉及适度运动通过抑制丝裂原活化蛋白激酶/细胞因子信号转导抑制因子3（MAPK/SOCS3）信号通路来减轻ERS，从而减轻HF诱导的骨骼肌萎缩。我们的研究阐明了适度运动在HF诱导的骨骼肌萎缩中的积极作用，揭示了其潜在的分子机制，并为HF中骨骼肌萎缩的综合治疗提供了新的科学依据。
