慢性肾脏病患者蛋白-能量消耗发生机制及干预的研究进展

Progress of research on pathogenesis and intervention of PEW in patients with CKD

慢性肾脏病(CKD)患者常伴有不同程度的蛋白-能量消耗(PEW),主要临床表现为骨骼肌萎缩,可增加患者并发症和死亡风险。PEW的发病机制是多因素的。研究认为食欲减退、泛素-蛋白酶体系(UPS)活化及细胞内胰岛素/胰岛素样生长因子-1(IGF-1)/磷脂酰肌醇激酶(P13K)/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。目前针对PEW采取的有效治疗方法为适当补充营养物质,保证足够热量和蛋白的摄入。此外,加强运动、及时纠正代谢性酸中毒和改善炎症状态也可对CKD患者骨骼肌萎缩起到预防和治疗作用。短期激素药物的使用可改善机体蛋白储存,但仍缺少关于其长期应用有效性和安全性的研究。而针对泛素-蛋白酶体系、肌抑素信号通路等肌萎缩分解代谢途径的有效阻断方法目前仍处于研究阶段,还需大量实验研究以寻找切实有效的预防或治疗措施。

Patients with chronic kidney disease （CKD） are often associated with different levels of protein-energy wasting （PEW） whose main clinical manifestation is skeletal muscle atrophy, which can increase the risk of complications and mortality. The pathogeuesis of PEW is muhifactorial. Previous studies suggested that loss of appetite, activation of the ubiquitin-proteasome system, and damage to the insulin/ insulin-like growth factor 1/phosphatidylinositol kinase/protein kinase B pathway were the main cause of muscle atrophy. With a lot of in-depth studies being finished in recent years, it has been found that inflammation, metabolic acidosis, hormone metabolism disorder, and myostatin expression increase also played important roles in the development and progress of muscle atrophy. At present, effective treatment for PEW is to add nutrients to ensure adequate intake of calories and protein. In addition, exercise, correction of metabolic acidosis, and improvement of inflammation in time also play roles in prevention and treatment of skeletal muscle atrophy in patients with CKD. Use of short-term hormone drugs can improve the body＇s protein storage, which lacks long-term researches on its efficacy and safety. It is still in the research stage to effectively block the catabolic pathways of skeletal muscle atrophy by targeting the ubiquitin proteasome system and myostatin signaling pathway, etc. A large number of experimental studies are still needed to explore effective measures for the prevention or treatment of PEW in patients with CKD.