SKELETAL-MUSCLE AND WHOLE-BODY PROTEIN-TURNOVER IN CARDIAC CACHEXIA - INFLUENCE OF BRANCHED-CHAIN AMINO-ACID ADMINISTRATION
SKELETAL-MUSCLE AND WHOLE-BODY PROTEIN-TURNOVER IN CARDIAC CACHEXIA - INFLUENCE OF BRANCHED-CHAIN AMINO-ACID ADMINISTRATION
复制标题
DOI：
10.1111/j.1365-2362.1988.tb01282.x
复制
发表时间：
1988-12-01
影响因子：
5.5
通讯作者：
RENNIE, MJ
中科院分区：
文献类型：
--
作者：
MORRISON, WL;GIBSON, JNA;RENNIE, MJ
肌肉蛋白消耗通常伴随严重心力衰竭。对8名平均体重下降19%的患者进行了所谓心脏恶病质机制的研究，并将结果与11名健康对照受试者进行了比较。酪氨酸和3 - 甲基组氨酸在腿部组织的交换分别用作净蛋白平衡和肌原纤维蛋白分解的特异性指标。采用以L - [1 - 13C]亮氨酸为示踪剂的稳定同位素标记技术测量全身蛋白质周转。与正常对照受试者相比，心脏恶病质患者腿部酪氨酸流出量（-8.1±0.6 nmol/100 ml腿部组织·min⁻¹对比 -4.2±0.3 nmol/100 ml·min⁻¹（P < 0.01））和3 - 甲基组氨酸流出量（-0.8±0.1 nmol/100 ml腿部组织·min⁻¹对比 -0.1±0.02 nmol/100 ml·min⁻¹（P < 0.005），均值±标准误）数值更大。结果表明，在心脏恶病质患者中，腿部组织的净负蛋白平衡状态与肌原纤维蛋白分解速率增加有关。在心脏恶病质中，将支链氨基酸（BCAA）输注至血浆浓度为1300±14 μmol/ml（即正常血浆值（282±11 μmol/ml）的4倍）时，酪氨酸（-8.4±0.7 nmol/100 ml腿部组织·min⁻¹）和3 - 甲基组氨酸（-1.0±0.2 nmol/100 ml腿部组织·min⁻¹）的流出量均无显著变化。同样，在正常受试者中，给予BCAA时酪氨酸流出量（-3.7±0.5 nmol/100 ml·min⁻¹）也未改变。然而，BCAA输注导致恶病质患者腿部组织中总氨基酸和酰胺氮净潴留，但在正常对照受试者中未出现这种情况。结果表明，BCAA对正常受试者或伴有肌肉消耗的心脏病患者的肌肉蛋白合成或分解没有急性影响，但可能促进氨基酸氮细胞内池的增加，这可能具有有益的长期效应。在心脏恶病质中，亮氨酸血浆通量成分（通过稳定同位素标记技术测定）与正常情况的差异表明，与正常相比，全身亮氨酸通量（蛋白质分解）、亮氨酸氧化和蛋白质合成均降低[79±24 μmol/kg·h⁻¹对比133±27 μmol/kg·h⁻¹（P < 0.0001）（均值±标准差），25±20对比40±10 μmol/kg·h⁻¹（P < 0.0001），以及54±7对比89±20 μmol/kg·h⁻¹（P < 0.0001）]。这些结果表明，尽管全身蛋白质周转总体下降，但在心脏恶病质中，这与腿部骨骼肌肌原纤维蛋白分解增加有关。
Muscle protein wasting commonly accompanies severe heart failure. The mechanism of this socalled cardiac cachexia has been investigated in eight patients with an average body weight decrement of 19%, whose results have been compared with those from 11 healthy control subjects. Exchanges of tyrosine and 3-methylhistidine across leg tissue were used as specific indicators of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using a stable isotope labelling technique with L-[1-13C] leucine as tracer. In patients with cardiac cachexia there were greater values, relative to those values in normal control subjects, of leg efflux of tyrosine (.sbd.8.1 .+-. 0.6 nmol 100 ml leg tissue-1 min-1 vs. .sbd.4.2 .+-. 0.3 nmol 100 ml-1 min-1 (P < 0.01)) and of 3-methylhistidine (-0.8 .+-. 0.1 nmol 100 ml leg tissue-1 min-1 vs. -0.1 .+-. 0.02 nmol 100 ml-1 min-1 (P < 0.005), mean .+-. SEM). The results suggest that in patients with cardiac cachexia the state of net negative protein balance across leg tissue is associated with an increased rate of myofibrillar protein breakdown. In cardiac cachexia, neither efflux of tyrosine (-8.4 .+-. 0.7 nmol 100 ml leg tissue-1 min-1) nor of 3-methylhistidine (-1.0 .+-. 0.2 nmol 100 ml leg tissue-1 min-1) were significantly altered by branched-chain amino acid (BCAA) infusion to plasma concentrations of 1300 .+-. 14 .mu.mol ml-1, i.e., four times normal plasma values (282 .+-. 11 .mu.mol ml-1). Similarly, in normal subjects, effluxes of tyrosine (-3.7 .+-. 0.5 nmol 100 ml-1 min-1) were unaltered by BCAA administration. Nevertheless, BCAA infusion caused a net retention of total amino and amide nitrogen in leg tissue of cachectic patients, but not in that of normal control subjects. The results suggest that BCAA have no acute effect on muscle protein synthesis or breakdown in normal subjects or in cardiac patients with muscle wasting, but may promote increases in the intracellular pool of amino acid nitrogen, which may have beneficial longer term effects. In cardiac cachexia, differences from normal in the components of the leucine plasma flux (determined by stable isotope labelling techniques) suggested that there was a depression in whole body leucine flux (protein breakdown), leucine oxidation and protein synthesis compared with normal [79 .+-. 24 .mu.mol kg-1 h-1 vs. 133 .+-. 27 .mu.mol kg-1 h-1 (P < 0.0001) (mean .+-. SD), 25 .+-. 20 vs. 40 .+-. 10 mol kg-1 h-1 (P < 0.0001), and 54 .+-. 7 vs. 89 .+-. 20 .mu.mol kg-1 h-1 (P < 0.0001), respectively]. These results suggest that although there is an overall depression of whole body protein turnover, in cardiac cachexia, this is associated with elevations of myofibrillar protein breakdown from skeletal muscle in the leg.