酒精性肝硬化伴肌肉减少症患者的肠外营养对骨骼肌蛋白周转率的影响。
Skeletal muscle protein turnover responses to parenteral nutrition in patients with alcoholic liver cirrhosis and sarcopenia.
机构信息
The Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital-Hvidovre Hospital, Copenhagen, Denmark.
出版信息
Am J Physiol Gastrointest Liver Physiol. 2023 Aug 1;325(2):G174-G183. doi: 10.1152/ajpgi.00242.2022. Epub 2023 Jun 20.
Alcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for 3 h of fasting followed by 3 h of intravenous PN (SmofKabiven 1,206 mL: amino acid = 38 g, carbohydrates = 85 g, and fat = 34 g) 4 mL/kg/h. We measured leg blood flow and sampled paired femoral arteriovenous concentrations and quadriceps muscle biopsies while providing a primed continuous infusion of [ring-d]-phenylalanine to quantify muscle protein synthesis and breakdown. Patients with ALC exhibited shorter 6-min walking distance (ALC: 487 ± 38 vs. controls: 722 ± 14 m, < 0.05), lower hand-grip strength (ALC: 34 ± 2 vs. controls: 52 ± 2 kg, < 0.05), and computed tomography (CT)-verified leg muscle loss (ALC: 5,922 ± 246 vs. controls: 8,110 ± 345 mm, < 0.05). Net leg muscle phenylalanine uptake changed from negative (muscle loss) during fasting to positive (muscle gain) in response to PN (ALC: -0.18 ± +0.01 vs. 0.24 ± 0.03 µmol/kg muscle·min; < 0.001 and controls: -0.15 ± 0.01 vs. 0.09 ± 0.01 µmol/kg muscle·min; < 0.001) but with higher net muscle phenylalanine uptake in ALC than controls ( < 0.001). Insulin concentrations were substantially higher in patients with ALC during PN. Our results suggest a higher net muscle phenylalanine uptake during a single infusion of PN in stable patients with ALC with sarcopenia compared with healthy controls. Muscle protein turnover responses to parenteral nutritional (PN) supplementation have not previously been studied in stable alcoholic liver cirrhosis (ALC). We applied stable isotope tracers of amino acids to directly quantify net muscle protein turnover responses to PN in sarcopenic males with ALC and healthy controls. We found a higher net muscle protein gain in ALC during PN, thereby providing the physiological rationale for future clinical trials of PN as a potential countermeasure to sarcopenia.
酒精性肝硬化(ALC)伴有肌肉减少症。本研究旨在探讨平衡肠外营养(PN)对 ALC 患者骨骼肌蛋白周转的急性影响。8 名男性 ALC 患者和 7 名年龄和性别匹配的健康对照者禁食 3 小时,然后静脉输注 PN(SmofKabiven 1,206 mL:氨基酸= 38 g,碳水化合物= 85 g,脂肪= 34 g)4 mL/kg/h,持续 3 小时。我们测量了腿部血流量,并采集了配对的股动静脉浓度和股四头肌活检,同时提供[ring-d]-苯丙氨酸的脉冲持续输注以定量肌肉蛋白质合成和分解。ALC 患者的 6 分钟步行距离更短(ALC:487±38 与对照:722±14 m,<0.05),握力更低(ALC:34±2 与对照:52±2 kg,<0.05),且 CT 证实腿部肌肉减少(ALC:5,922±246 与对照:8,110±345 mm,<0.05)。在 PN 作用下,空腹时腓肠肌的苯丙氨酸摄取呈负值(肌肉损失),转变为正值(肌肉获得)(ALC:-0.18±+0.01 与 0.24±0.03 μmol/kg 肌肉·min;<0.001 和对照:-0.15±+0.01 与 0.09±0.01 μmol/kg 肌肉·min;<0.001),但 ALC 患者的净肌肉苯丙氨酸摄取高于对照组(<0.001)。PN 期间,ALC 患者的胰岛素浓度明显升高。我们的结果表明,与健康对照组相比,稳定期伴有肌肉减少症的 ALC 患者单次 PN 输注时的净肌肉苯丙氨酸摄取更高。肌肉蛋白周转对肠外营养(PN)补充的反应以前尚未在稳定的酒精性肝硬化(ALC)患者中进行研究。我们应用氨基酸稳定同位素示踪剂直接定量 PN 对 ALC 患者和健康对照组的净肌肉蛋白周转的反应。我们发现 ALC 患者在 PN 期间的净肌肉蛋白获得更高,从而为 PN 作为肌肉减少症潜在对策的未来临床试验提供了生理学依据。