Optimal Dosing Regimen to Recover from Muscle Atrophy

从肌肉萎缩中恢复的最佳剂量方案

• 批准号: 10382211
• 负责人: Richard L. Lieber
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382211
• 关键词: Address; Aging; Analysis of Variance; Area; Atrophic; Bed rest; Cachexia; Catabolic Process; Chronic Disease; Clinical; Craniocerebral Trauma; Data; Data Analyses; Denervation; Disease; Dose; Drug Industry; Drug Prescriptions; Duchenne muscular dystrophy; Equilibrium; Event; Exercise Therapy; Experimental Designs; Experimental Models; Exposure to; Fatty acid glycerol esters; Female; Financial Hardship; Gene Expression; Generations; Genetic; Glucocorticoids; Goals; Grant; Growth; Health; Hindlimb Suspension; Human; Immobilization; Inflammatory; Injury; Intake; Intervention; Limb structure; Maintenance; Malignant Neoplasms; Measures; Mechanics; Metabolic Pathway; Modeling; Mus; Muscle; Muscle function; Muscular Atrophy; Muscular Dystrophies; Neurodegenerative Disorders; Neuromuscular Diseases; Obesity; Orthopedics; Osteoporosis; Pathway interactions; Performance; Pharmaceutical Preparations; Physical Performance; Physical therapy; Prednisone; Protocols documentation; Quality of life; Randomized; Recovery; Regimen; Reporting; Rheumatoid Arthritis; Risk Factors; Skeletal Muscle; Steroids; Stroke; Structure; Testing; Trauma; Veterans; Wild Type Mouse; care systems; cost; design; experience; experimental study; healing; human study; improved; injury recovery; limb injury; male; military veteran; muscle form; neurovascular; novel; nutrition; optimal treatments; prevent; reduced muscle mass; side effect; skeletal muscle wasting; treatment effect

Skeletal muscle atrophy in the Veteran population is extremely common and may arise due to poor nutrition, denervation, head injury, limb trauma, cancer, ageing, and disuse. Atrophy results from mechanical unloading of muscle over a prolonged period, resulting in reduced muscle mass, area, and strength (without a reduction of myofibers) and can be disabling. For almost a century it has been known that transient exposure to glucocorticoids (GC) enhances physical performance and increases endurance. Paradoxically, despite these performance enhancing benefits, GC are not routinely prescribed for non-inflammatory diseases since standard daily GC dosing regimens cause marked muscle atrophy. In this SPiRE grant, we will test the hypothesis that once-weekly steroid administration in a muscle atrophy model improves muscle function and growth. Muscle atrophy will be induced in mice by cast immobilization, as prolonged casting is a common event that induces atrophy in Veterans and does not disrupt neurovascular structures. The experimental design is a two-way ANOVA model with seven groups of mice, randomized with equal numbers of male and female mice (n=6 mice total per group). Mice will be dosed with 0.1mg/kg or 1mg/kg of prednisone steroid during casting, post casting (recovery) or both during casting and during recovery. PBS “dosing” will be used as a control. Muscle force generation, gene expression, size, endurance capacity and muscle mass measured after each of these treatments. The data generated from this SPiRE grant will enable design of a human study that refines these treatments in the Veteran population.

骨骼肌萎缩在退伍军人人群中是非常常见的，可能会出现由于穷人 营养、去神经支配、头部损伤、肢体创伤、癌症、衰老和废用。萎缩的原因是 肌肉长时间的机械卸载，导致肌肉质量、面积和 力量（没有减少肌纤维），并可能致残。近世纪来， 已知短暂暴露于糖皮质激素（GC）增强身体表现并增加 耐力奇怪的是，尽管有这些性能增强的好处，GC并不经常 由于标准每日GC给药方案会引起显著的 肌肉萎缩在这个SPiRE补助金，我们将测试的假设，每周一次类固醇管理 在肌肉萎缩模型中改善肌肉功能和生长。肌肉萎缩会被诱导， 由于长时间的石膏固定是诱发退伍军人萎缩的常见事件， 并且不破坏神经血管结构。实验设计为双因素方差分析模型 用7组小鼠，随机分配相同数量的雄性和雌性小鼠（总共n=6只小鼠 每组）。在浇铸期间，将对小鼠给药0.1mg/kg或1 mg/kg泼尼松类固醇， 铸造（恢复）或在铸造期间和在恢复期间两者。PBS“给药”将用作对照。 肌肉力量的产生，基因表达，大小，耐力和肌肉质量测量后， 每一种治疗方法。从SPiRE赠款产生的数据将使人类的设计成为可能。 一项在退伍军人群体中改进这些治疗方法的研究。