慢性肾脏病诱导骨骼肌萎缩的发病机制

Muscle wasting associated chronic kidney disease

慢性肾脏病(CKD)患者常伴难纠正的进行性蛋白-能量消耗(PEW),临床主要表现骨骼肌萎缩。肌萎缩的发病机制很复杂,常由多因素共同作用所致。既往研究认为食欲减退、泛素-蛋白酶体系活化及细胞内胰岛素/胰岛素样生长因子1/磷脂酰肌醇激酶/蛋白激酶B信号通路受损是导致肌萎缩的主要原因。然而随着近年大量深入研究,发现炎症反应、代谢性酸中毒、激素代谢紊乱和肌抑素表达增加等因素在肌萎缩发生发展中也起着不可忽视的作用,但其中部分作用机制尚未完全阐明,需深入探索,以寻找切实有效的干预靶点,改善CKD患者临床预后。

The patients with chronic kidney disease usually have progressive protein-energy waste, which increases the morbidity and mortality. Most body stores of protein are in skeletal muscle, the protein depletion presents itself as loss of muscle mass, or muscle atrophy. The pathogenesis of muscle wasting is very complex, which is usually caused by muhifactors. Previous studies showed that anorexia, activation of the ATP-dependent ubiquitin-proteasome system and defects in insulin/insulin-like growth factor 1 （IGF-1）/PI3K/Akt intraeellular signaling processes accelerated muscle protein degradation, deereased protein synthesis, and caused the muscle atrophy. Recent studies found that elevated levels of eytokines, metabolic acidosis, increased levels of myostatin and glucoeortieoid also play an important role in causing muscle wasting. Some of their mechanisms are not clear,and more studies are needed for finding effective treatment to improve the outcome of patients with CKD.