REDOX MODULATION OF MUSCLE FUNCTION IN MICROGRAVITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。美国宇航局的关键路径路线图将骨骼肌功能的丧失确定为国际空间站、月球和火星长期任务的关键问题。重力卸荷导致肌肉萎缩和收缩功能障碍导致反重力肌无力。在特定条件下，特别是舱外活动（EVA），机组人员的表现也可能受到肌肉疲劳的限制。基于地面的研究表明，在卸载和剧烈运动两种情况下，氧化应激都会导致肌肉功能的丧失，而抗氧化预处理可以保护肌肉功能。这个实验模型是我们当前项目的基础。实验将评估一种有潜力对抗骨骼肌氧化应激和防止机组人员肌肉疲劳的药理学制剂。实验方法显然是务实的，旨在确定和制定在近中期进行人体检测的对策。该项目中测试的化合物的功效得到了动物研究和人体试验的初步数据的支持，目前已被批准用于人体全身给药。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. NASA's Critical Path Roadmap identifies loss of skeletal muscle function as a key concern for long-term missions to the International Space Station, the Moon, and Mars. Gravitational unloading causes weakness of antigravity muscles due to loss of muscle mass (atrophy) and contractile dysfunction. In selected conditions, especially extravehicular activity (EVA), crewmember performance can also be limited by muscle fatigue. Ground-based studies suggest that oxidative stress contributes to loss of muscle function in both conditions, unloading and strenuous exercise, and that antioxidant pretreatment can protect muscle function. This experimental model is the basis for our current project. Experiments will evaluate a pharmacologic agent that has the potential to oppose oxidative stress in skeletal muscle and protect against muscle fatigue in flight crews. The experimental approach is explicitly pragmatic, designed to identify and develop countermeasures for human testing in the near-to-mid term. The efficacy of the compound tested in this project is supported by preliminary data from animal studies and human trials and is currently approved for systemic administration to humans.