Anabolic Agents and Muscle Protein in Burned Children

这项建议的目的是调查一般假设，重组生长激素和/或氧雄酮(睾酮)将增加骨骼肌蛋白质的净合成和减少细胞内氨基酸的净流出在烧伤后的儿童。这个项目的另一个目标是研究这样一种假设，即这些合成代谢药物的影响将通过增加向内的氨基酸运输而被放大。促进氨基酸向内转运的干预措施，如氨基酸输注，或合成效率，如运动，将在给予这些合成代谢药的同时进行调查。最后，我们将研究改善高皮质醇血症将减少肌肉蛋白质分解的假说，并与这些合成代谢药物一起导致更大的蛋白质净平衡。这项建议将评估这些合成代谢药物的疗效，并确定未来干预研究的方向。为了同时量化肌肉蛋白质合成和分解的速率，将使用一个新的模型，该模型包括使用稳定同位素标记的氨基酸示踪剂以及测量细胞内游离和蛋白质结合的氨基酸富集量。这种独特的方法可以在体内直接测定骨骼肌中肌肉蛋白质的合成和分解。我们还将利用第二个依赖于动脉-静脉差异的模型来独立确定肌肉蛋白质的合成、分解和组织氨基酸运输。这种方法学的结合使我们能够独立地确认这些拟议的干预措施对肌肉蛋白质的影响。此外，我们将确定对肌原纤维和线粒体蛋白质组分的反应的干预效应。综合代谢制剂对烧伤儿童肌肉蛋白质合成的影响将通过比较标准护理和通过明确的“室内”锻炼计划康复的儿童来评估。此外，我们将讨论烧伤后9个月儿童急性合成代谢药物和运动对骨骼肌蛋白质合成和分解以及氨基酸动力学的交互影响。这些研究将深入了解合成代谢物质、氨基酸和运动对这一独特人群的合成机制的影响。

The goal of this proposal is to investigate the general hypothesis that recombinant growth hormone and/or oxandrolone (testosterone) will increase net skeletal muscle protein synthesis and decrease the net efflux of intracellular amino acids in recovering burned children. A further goal of this project is to investigate the hypothesis that the effects of these anabolic agents will be amplified by increased inward amino acid transport. Interventions promoting inward amino acid transport, such as amino acid infusion, or synthetic efficiency, such as exercise, will be investigated in conjunction with administration of these anabolic agents. Finally, we will investigate the hypothesis that amelioration of hyper- coritsolemia will reduce muscle protein breakdown and result in a greater net protein balance with these anabolic agents. This proposal will evaluate the efficacy of these anabolic agents and determine the direction of future intervention studies. In order to simultaneously quantify the rates of muscle protein synthesis and breakdown, a new model will be used that involves the use of tracers of amino acids labeled with stable isotopes and the measurement of intracellular free and protein-bound amino acid enrichments. This unique methodology allows the direct determination in vivo of muscle protein synthesis and breakdown in skeletal muscle. We will also utilize a second model that relies on arterial-venous differences to independently determine muscle protein synthesis, breakdown, and tissue amino acid transport. This combination of methodologies allows us to independently confirm the effects of these proposed interventions on muscle protein. In addition, we will determine interventional effects on the responses of myofibrillar and mitochondrial protein fractions. The effects of anabolic agents on muscle protein synthesis in burned children will be assessed by comparing standard care to children rehabilitated with a defined "in-house" exercise program. Further, we will address the interactive effects of acute anabolic agents and exercise on skeletal muscle protein synthesis and breakdown, and amino acid kinetics in children 9 months post-burn. These studies will provide insight into the synthetic mechanisms affected by anabolic agents, amino acids and exercise in this unique population.