Muscle Regrowth during Physical Rehabilitation and Amino Acid Supplementation

简介(申请人提供)：本建议的目的是为了促进候选人S在翻译和临床研究方面的科学发展，并使他能够过渡到康复领域的独立翻译科学家。俄勒冈大学提供了优秀的学术和研究环境和基础设施，为候选人S进行翻译研究的教育和培训提供了便利。 职业目标：该奖项将支持候选人S成功地从初级研究员转变为中级独立研究员，提供一系列正式和非正式的职业发展活动，以及一个在杰出指导团队的监督下实践学习和获取重要初步数据的研究项目。具体的短期职业目标将包括肌肉新陈代谢、稳定同位素技术和康复研究的培训；负责任地进行研究和其他标准科学技能的培训；为获得实用的临床研究技能和为今后康复科学的研究应用提供初步数据而进行的研究性研究。长期的科学目标是让候选人成为骨骼肌新陈代谢和康复方面的专家，并继续为医学研究提供资金。 研究计划：一般的假设是，老年人在急性肌肉骨骼应激后的肌肉再生将受到传统身体康复的积极影响，并通过营养补充进一步增强。使用最先进的稳定同位素方法研究肌肉代谢和测量细胞信号，我们将检验下列特定假设：1)确定TKR手术中缺血再灌注损伤对骨骼肌细胞信号和基因表达的影响；1)确定肌肉细胞信号和基因表达的急性变化是否与2周后MRI测量的肌肉萎缩相关；2)确定TKA后摄入EAA是否显著增加肌肉蛋白质合成；3)确定在PT康复期间补充EAA对TKA前后肌肉质量、力量和功能的影响。 公众利益：这项研究将把康复工作的重点放在具体的、目前尚未解决的导致老年人全膝关节置换后肌肉丧失的机制上。虽然膝关节置换术后由于骨性关节炎引起的膝关节疼痛通常会得到缓解，但完全恢复身体功能和独立是很难实现的。这项研究将有助于恢复快速增长的膝关节炎老年人口的身体功能和独立性。

DESCRIPTION (provided by applicant): The purpose of this proposal is to further the candidate?s scientific development in translational and clinical research and to make possible his transition to become an independent translational scientist in rehabilitation. The University of Oregon provides an outstanding academic and research environment and infrastructure to facilitate the candidate?s education and training in the conduct of translational research. Career Goals: This award will support the candidate?s successful transition from a junior researcher into a mid level independent investigator by providing an array of formal and informal career development activities, and a research project for hands-on learning and acquisition of essential preliminary data under the supervision of an exceptional mentoring team. The specific short-term career goals will include training in muscle metabolism, stable isotope techniques and rehabilitation research; training in the responsible conduct of research and other standard scientific skills; performance of a research study for the acquirement of practical clinical research skills and of preliminary data for future research applications in rehabilitation science. The long-term scientific goal is for the candidate to become an expert in skeletal muscle metabolism and rehabilitation with continuous funding for medical research. Research Plan: The general hypothesis is that in older adults muscle regrowth after an acute musculoskeletal stress will be positively influenced by traditional physical rehabilitation, and further enhanced by nutritional supplementation. Using state-of-the-art stable isotope methodologies for the study of muscle metabolism and methodologies for the measurement of cell signaling, we will test the following specific hypotheses: 1a) To determine the effects of ischemia-reperfusion injury on cell signaling and gene expression in skeletal muscle during TKR surgery; 1b) To determine if acute changes in muscle cell signaling and gene expression correlate with muscle atrophy measured 2 weeks later by MRI; 2) To determine if muscle protein synthesis is acutely increased with the ingestion of EAA following TKA; 3) To determine the effects of EAA Supplementation during PT rehabilitation on muscle mass, strength, and function before and after TKA. Public Benefit: This research will focus rehabilitation efforts on specific and currently unresolved mechanisms responsible for muscle loss following total knee replacement in older adults. While knee pain due to bone arthritis is often alleviated after knee replacement, complete return of physical function and independence is difficult to achieve. This research will help to restore physical function and independence in the rapidly growing population of older adults with knee arthritis.