骨骼肌质量维持的分子机制涉及多种信号通路之间的相互作用。在正常生理条件下，相互交叉的信号通路用于控制和协调骨骼肌肥大和萎缩，最终使肌肉蛋白质合成和降解之间达到平衡。当蛋白质合成的总速率超过蛋白质降解的速率时，肌肉逐渐肥大，而当蛋白质合成的总速率低于蛋白质降解的速率时，肌肉则发生萎缩。肌细胞萎缩中主要涉及两种蛋白质降解途径，即泛素(ubiquitin，Ub)-蛋白酶体途径和自噬-溶酶体途径(autophagy-lysosomalpathway，ALP)。蛋白质降解途径在肌肉萎缩期间被激活，导致肌肉质量的损失。肌肉萎缩可在营养不良、衰老以及恶病质等多种条件下出现，骨科疾病引发的骨骼肌萎缩主要包括骨折导致的失用性肌萎缩以及去神经性肌萎缩。控制和协调骨骼肌蛋白质合成及降解的信号通路包括胰岛素样生长因子 1(insulin-like growth factor 1，IGF1)-Akt-哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin，mTOR)、肌生长抑制素(myostatin)-激活素 A(activin A)-Smad、G蛋白 α抑制活性多肽2(G protein α inhibitory peptide 2，Gαi2)-PKC、核因子 κB(nuclear factor κB，NF-κB)、外胚层发育不良 A2 受体(ectodysplasin A2 receptor，EDA2R)-NF-κB 诱导激酶(NF-κB inducing kinase，NIK)、丝裂原活化蛋白激酶(mitogen-activated protein kinase，MAPK)信号通路。本文综述了骨骼肌发生萎缩时蛋白质的降解途径及调节肌萎缩蛋白质降解的相关信号通路。
Research progress on molecular mechanism related to skeletal muscle atrophy
The maintenance of skeletal muscle quality involves various signal pathways that interact with each other.Under normal physiological conditions,these intersecting signal pathways regulate and coordinate the hypertrophy and atrophy of skeletal muscles,balancing the protein synthesis and degradation of muscle.When the total rate of protein synthesis exceeds that of protein degrada-tion,the muscle gradually becomes enlarged,while when the total rate of protein synthesis is lower than that of protein degradation,the muscle shrinks.Myocyte atrophy mainly involves two protein degradation pathways,namely ubiquitin-proteasome and autophagy-lysosome.Protein degradation pathway is activated during muscle atrophy,resulting in the loss of muscle mass.Muscle at-rophy can occur under various conditions such as malnutrition,aging and cachexia.Skeletal muscle atrophy caused by orthopedic dis-eases mainly includes disuse muscular atrophy caused by fracture and denervation muscular atrophy.The signal pathways that control and coordinate protein synthesis and degradation in skeletal muscle include insulin-like growth factor 1(IGF1)-Akt-mammalian tar-get of rapamycin(mTOR),myostatin-activin A-Smad,G protein α inhibitory peptide 2(Gαi2)-PKC,nuclear factor κB(NF-κB),ecto-dysplasin A2 receptor(EDA2R)-NF-κB inducing kinase(NIK)and mitogen-activated protein kinase(MAPK)pathways.This paper provides a comprehensive review of the protein degradation pathways in skeletal muscle atrophy and the associated signal pathways regulating protein degradation in muscular atrophy.
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