Impact of Aerobic Training on Transcriptomic Changes in Skeletal Muscle of Rats with Cardiac Cachexia

Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60mg/Kg). Aerobic training consisted of treadmill running for 30min at ~55% of maximal capacity, 5x/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA sequencing analysis was per-formed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs compared to their respective controls. GO enrichment, pathway enrichment, and weighted gene co-expression network analysis (WGCNA) identified key DEGs as po-tential hub genes involved in disrupted lipid metabolism and muscle remodeling in sedentary CC rats, which were not observed in the exercised CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid me-tabolism and muscle remodeling in rats with CC, highlighting its therapeutic potential.心脏恶病质（Cardiac cachexia, CC）是心力衰竭（heart failure, HF）的晚期阶段，以骨骼肌结构与功能异常为特征，进而引发肌肉丢失。有氧运动训练可带来获益，但其背后的分子机制仍未得到充分阐明。本研究旨在探讨有氧运动训练对恶病质骨骼肌中与疾病进展相关的转录组变化的治疗作用。本研究通过单次注射野百合碱（60mg/kg）构建雄性Wistar大鼠心力衰竭模型。有氧运动训练方案为：在跑台以最大摄氧量约55%的强度持续跑步30分钟，每周5次，共持续4周。评估内容包括体质量、右心室质量、骨骼肌纤维直径以及运动耐量。对腓肠肌内侧头进行RNA测序（RNA sequencing）分析。与各自对照组相比，久坐不动的恶病质大鼠存在114个差异表达基因（differentially expressed genes, DEGs），而进行有氧运动训练的恶病质大鼠仅存在18个差异表达基因。基因本体（Gene Ontology, GO）富集分析、通路富集分析以及加权基因共表达网络分析（weighted gene co-expression network analysis, WGCNA）结果显示，久坐心脏恶病质大鼠中的关键差异表达基因可作为潜在枢纽基因，参与脂质代谢紊乱与肌肉重塑过程，而该现象在接受有氧运动训练的心脏恶病质大鼠中并未出现。上述研究结果表明，有氧运动训练可缓解心脏恶病质大鼠体内与脂质代谢及肌肉重塑相关的转录组改变，凸显了其治疗潜力。