Löfberg E, Essén P, McNurlan M, Wernerman J, Garlick P, Anderstam B, Bergström J, Alvestrand A
Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
Clin Nephrol. 2000 Oct;54(4):284-94.
Earlier studies have shown that hemodialysis (HD) treatment stimulates net protein catabolism. Several factors associated with HD affect protein catabolism, such as an inflammatory effect due to blood-membrane contact and loss of amino acids and glucose into the dialysate.
SUBJECTS, MATERIAL AND METHODS: We have studied protein synthesis in skeletal muscle of healthy volunteers (n = 9) before and after a single heparin-free HD. Protein synthesis (PS) was studied, using 2 independent techniques: the incorporation of labeled 2H5-phenylalanine into muscle protein, which gives a quantitative measure of the fractional synthesis rate of muscle proteins, and the concentration and size distribution of ribosomes, which gives a qualitative estimate of protein synthesis. Furthermore, free amino acid concentrations were determined in muscle and plasma.
The rate of PS, expressed as the fractional synthesis rate, decreased by 13% during HD (p < 0.02). The capacity for PS, as reflected by the total concentration of ribosomes, was reduced by 22% (p < 0.02) and the activity of PS, expressed as the relative proportion of polyribosomes, decreased from 48.4 +/- 0.9% to 44.8 +/- 0.8% after dialysis (p < 0.01). There was a total loss of 5.8 +/- 0.3 g amino acid to the dialysate. Plasma and muscle free amino acid concentrations were determined at four time points; before and after the phenylalanine incorporation period, before dialysis and before and after the second incorporation period after dialysis. Immediately after dialysis, there was a decrease in plasma asparagine, histidine, alanine, taurine, valine and tryptophane. In muscle, no changes occurred except for a slight increase in leucine after dialysis. In blood, the glucose concentration decreased and the total amount of glucose lost to the dialysate was 21 +/- 3.0 g. In summary, one single hemodialysis treatment decreases fractional protein synthesis rate in skeletal muscle.
The results demonstrate substantial losses of amino acids and glucose to the dialysate and decreased amino acid concentrations in plasma, but only minimal changes in the intracellular amino acid concentrations in muscle, suggesting that the decreased PS is caused not by lack of amino acid precursors at the site of the synthesis activity, but by other mechanisms.
早期研究表明,血液透析(HD)治疗会刺激净蛋白分解代谢。与血液透析相关的几个因素会影响蛋白分解代谢,比如血液与膜接触产生的炎症效应以及氨基酸和葡萄糖流失到透析液中。
对象、材料与方法:我们研究了9名健康志愿者在单次无肝素血液透析前后骨骼肌中的蛋白合成情况。采用两种独立技术研究蛋白合成(PS):将标记的2H5-苯丙氨酸掺入肌肉蛋白中,以此定量测定肌肉蛋白的分数合成率;以及核糖体的浓度和大小分布,以此定性评估蛋白合成。此外,还测定了肌肉和血浆中的游离氨基酸浓度。
以分数合成率表示的蛋白合成速率在血液透析期间下降了13%(p < 0.02)。以核糖体总浓度反映的蛋白合成能力降低了22%(p < 0.02),以多核糖体相对比例表示的蛋白合成活性在透析后从48.4±0.9%降至44.8±0.8%(p < 0.01)。有5.8±0.3克氨基酸总共流失到透析液中。在四个时间点测定了血浆和肌肉中的游离氨基酸浓度;苯丙氨酸掺入期前后、透析前以及透析后第二个掺入期前后。透析后即刻,血浆中天冬酰胺、组氨酸、丙氨酸、牛磺酸、缬氨酸和色氨酸浓度下降。在肌肉中,除了透析后亮氨酸略有增加外,未发生变化。血液中,葡萄糖浓度下降,流失到透析液中的葡萄糖总量为21±3.0克。总之,单次血液透析治疗会降低骨骼肌中的分数蛋白合成率。
结果表明氨基酸和葡萄糖大量流失到透析液中,血浆中氨基酸浓度降低,但肌肉细胞内氨基酸浓度仅有微小变化,这表明蛋白合成速率降低并非由合成活性部位缺乏氨基酸前体所致,而是由其他机制引起。