England B K, Price S R
Renal Division, Emory University School of Medicine, Atlanta, Ga., USA.
Blood Purif. 1995;13(3-4):147-52. doi: 10.1159/000170197.
Malnutrition and a loss of lean body mass frequently complicate chronic renal failure. Muscle wasting in uremia is caused by increased protein degradation, decreased protein synthesis and increased branched-chain amino acid oxidation. Acidosis and glucocorticoids are pivotal in these pathophysiologic aberrations. When the acidosis of chronic renal failure is corrected by feeding bicarbonate, protein degradation and amino acid oxidation normalize. Likewise, if patients and animals with normal renal function are made acidotic, protein degradation and amino acid oxidation increase. In adrenalectomized, acidotic rats, proteolysis increases only when they are supplemented with physiologic concentrations of glucocorticoids, suggesting that glucocorticoids are necessary for increased proteolysis. Acidosis stimulates the ATP-dependent proteolytic process involving ubiquitin and the 26S proteasome. Thus, acidosis evokes a glucocorticoid-dependent catabolic response in muscle that can account for the protein wasting associated with uremia.
营养不良和瘦体重丢失常使慢性肾衰竭复杂化。尿毒症中的肌肉萎缩是由蛋白质降解增加、蛋白质合成减少以及支链氨基酸氧化增加所致。酸中毒和糖皮质激素在这些病理生理异常中起关键作用。通过给予碳酸氢盐纠正慢性肾衰竭的酸中毒时，蛋白质降解和氨基酸氧化恢复正常。同样，如果肾功能正常的患者和动物发生酸中毒，蛋白质降解和氨基酸氧化会增加。在肾上腺切除的酸中毒大鼠中，只有在补充生理浓度的糖皮质激素时蛋白水解才会增加，这表明糖皮质激素是蛋白水解增加所必需的。酸中毒刺激涉及泛素和26S蛋白酶体的ATP依赖性蛋白水解过程。因此，酸中毒在肌肉中引发糖皮质激素依赖性分解代谢反应，这可以解释与尿毒症相关的蛋白质消耗。
