线粒体功能障碍在心衰后骨骼肌萎缩中的机制研究OA

Mitochondrial dysfunction has gained considerable attention in recent years as a central contributor to peripheral skeletal muscle atrophy secondary to heart failure(HF).In skeletal muscle from patients with HF,im-paired mitochondrial energy production,excessive accumulation of reactive oxygen species(ROS),disrupted calci-um homeostasis,mitochondrial DNA(mtDNA)mutations,imbalanced mitochondrial dynamics(abnormal fusion and fission),dysregulated mitophagy,activation of apoptotic pathways,and reduced mitochondrial biogenesis have all been implicated as key mechanisms driving post-HF myofiber wasting.Broadly,the mitochondrial derangements that promote skeletal muscle atrophy after HF operate through two non-mutually exclusive pathways:cardiac im-pairment caused by HF that secondarily induces skeletal muscle dysfunction;direct alterations within skeletal mus-cle triggered by HF-associated factors such as disuse,hypoxia,and systemic metabolic disturbances.Both pathways exacerbate metabolic abnormalities in muscle.Nevertheless,important mechanistic uncertainties remain.This re-view summarizes current evidence linking mitochondrial dysfunction to skeletal muscle atrophy following HF and discusses how distinct dimensions of mitochondrial impairment influence the development and progression of muscle wasting,with the aim of providing a theoretical basis for strategies to prevent and treat muscle atrophy in patients with HF.