Franch H A, Mitch W E
Renal Division, Emory University School of Medicine, Atlanta, Georgia, USA.
J Am Soc Nephrol. 1998 Dec;9(12 Suppl):S78-81.
Chronic metabolic acidosis stimulates the catabolism of bone and muscle in experimental animals and humans. The toxicity caused by acidosis involves changes in endocrine function and toxicity arising from the homeostatic responses that are activated by the body to maintain pH near normal levels. Glucocorticoids, insulin, insulin-like growth factor-1, and parathyroid hormone play important roles in the homeostatic responses of bone and muscle to acid. Bone buffering of acid and the resulting increase in renal calcium excretion leads to negative calcium balance. Activation of the ubiquitin-proteasome proteolytic system and branched-chain ketoacid dehydrogenase in muscle, along with hepatic glutamine synthesis in the liver and renal glutamine uptake, are homeostatic mechanisms that cause negative nitrogen balance and loss of muscle mass. Treating the acidosis of chronic renal insufficiency improves both bone and muscle metabolism by reducing the loss of calcium and protein and amino acids in the two organs, respectively. Thus, treating acidosis suppresses both bone and muscle catabolism in patients with normal and reduced renal function.
慢性代谢性酸中毒会刺激实验动物和人类骨骼与肌肉的分解代谢。酸中毒所导致的毒性涉及内分泌功能的变化以及机体为维持pH值接近正常水平而激活的稳态反应所产生的毒性。糖皮质激素、胰岛素、胰岛素样生长因子-1和甲状旁腺激素在骨骼和肌肉对酸的稳态反应中发挥重要作用。骨骼对酸的缓冲作用以及由此导致的肾钙排泄增加会导致钙负平衡。肌肉中泛素-蛋白酶体蛋白水解系统和支链酮酸脱氢酶的激活，以及肝脏中肝谷氨酰胺的合成和肾脏对谷氨酰胺的摄取，都是导致负氮平衡和肌肉量流失的稳态机制。治疗慢性肾功能不全的酸中毒可分别减少两个器官中钙以及蛋白质和氨基酸的流失，从而改善骨骼和肌肉代谢。因此，治疗酸中毒可抑制肾功能正常和降低的患者的骨骼和肌肉分解代谢。
