Anabolic Agents and Muscle Protein in Burned Children

本研究的目的是研究一种普遍的假设，即重组生长激素和/或羟雄酮（睾酮）会增加烧伤恢复儿童骨骼肌蛋白的净合成，减少细胞内氨基酸的净流出。该项目的另一个目标是研究这样一种假设，即这些合成代谢剂的作用将被增加的向内氨基酸运输放大。促进氨基酸向内转运的干预措施，如氨基酸输注，或促进合成效率的干预措施，如运动，将与这些合成代谢剂的施用一起进行研究。最后，我们将研究高皮质醇血症的改善将减少肌肉蛋白质分解并导致与这些合成代谢剂之间更大的净蛋白质平衡的假设。该建议将评估这些合成代谢药物的功效，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，将使用一种新的模型，该模型涉及使用用稳定同位素标记的氨基酸示踪剂和测量细胞内游离和蛋白质结合的氨基酸富集。这种独特的方法可以直接测定骨骼肌中肌肉蛋白质的合成和分解。我们还将利用第二种模型，该模型依赖于动静脉差异来独立确定肌肉蛋白质合成、分解和组织氨基酸运输。这些方法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的影响。此外，我们将确定介入对肌原纤维和线粒体蛋白组分反应的影响。合成代谢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定义“内部”运动计划的儿童康复来评估。此外，我们将讨论急性合成代谢剂和运动对烧伤后9个月儿童骨骼肌蛋白质合成和分解以及氨基酸动力学的相互作用。这些研究将为这一独特人群中受合成代谢剂、氨基酸和运动影响的合成机制提供见解。

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.