Department of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester, Leicester, LE1 9HN, UK.
Eur J Appl Physiol. 2013 Aug;113(8):2111-24. doi: 10.1007/s00421-013-2628-5. Epub 2013 Apr 17.
Muscle-wasting in chronic kidney disease (CKD) arises from several factors including sedentary behaviour and metabolic acidosis. Exercise is potentially beneficial but might worsen acidosis through exercise-induced lactic acidosis. We studied the chronic effects of exercise in CKD stage 4-5 patients (brisk walking, 30 min, 5 times/week), and non-exercising controls; each group receiving standard oral bicarbonate (STD), or additional bicarbonate (XS) (Total n = 26; Exercising + STD n = 9; Exercising +XS n = 6; Control + STD n = 8; Control + XS n = 3). Blood and vastus lateralis biopsies were drawn at baseline and 6 months. The rise in blood lactate in submaximal treadmill tests was suppressed in the Exercising + XS group. After 6 months, intramuscular free amino acids (including the branched chain amino acids) in the Exercising + STD group showed a striking chronic depletion. This did not occur in the Exercising + XS group. The effect in Exercising + XS patients was accompanied by reduced transcription of ubiquitin E3-ligase MuRF1 which activates proteolysis via the ubiquitin-proteasome pathway. Other anabolic indicators (Akt activation and suppression of the 14 kDa actin catabolic marker) were unaffected in Exercising + XS patients. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methylhistidine output) was not observed. It is suggested that alkali effects in exercisers arose by countering exercise-induced acidosis. Whether further anabolic effects are attainable on combining alkali with enhanced exercise (e.g. resistance exercise) merits further investigation.
慢性肾脏病（CKD）患者会出现肌肉减少症，其发病原因包括久坐不动的行为方式和代谢性酸中毒。运动可能有益，但由于运动引起的乳酸酸中毒，运动可能会使酸中毒恶化。我们研究了 CKD 4-5 期患者（快走，30 分钟，每周 5 次）和不运动对照组患者接受慢性运动的影响；每组患者均接受标准口服碳酸氢盐（STD）或额外碳酸氢盐（XS）治疗（总例数=26；运动+STD 组 n=9；运动+XS 组 n=6；对照组+STD 组 n=8；对照组+XS 组 n=3）。在基线和 6 个月时采集血液和股外侧肌活检。在亚最大跑步机测试中，运动+XS 组的血乳酸升高受到抑制。6 个月后，运动+STD 组的肌肉内游离氨基酸（包括支链氨基酸）出现明显的慢性消耗。运动+XS 组未发生这种情况。运动+XS 患者的这种变化伴随着泛素 E3 连接酶 MuRF1 的转录减少，MuRF1 通过泛素-蛋白酶体途径激活蛋白水解。运动+XS 患者的其他合成代谢指标（Akt 激活和 14kDa 肌动蛋白分解代谢标志物的抑制）不受影响。可能由于这个原因，未观察到肌原纤维蛋白水解的整体抑制（3-甲基组氨酸的产生）。研究提示，运动者的碱效应是通过中和运动引起的酸中毒而产生的。在结合碱和增强运动（如抗阻运动）的情况下是否能获得进一步的合成代谢作用，值得进一步研究。
