Optimal Dosing Regimen to Recover from Muscle Atrophy

骨骼肌萎缩在退伍军人中非常常见，可能是由于贫穷而引起的 营养、去神经、头部损伤、肢体创伤、癌症、衰老和停用。萎缩由以下原因引起 在长时间内机械地卸载肌肉，导致肌肉质量、面积和 强度(不会减少肌纤维)，并可禁用。近一个世纪以来，它一直是 已知，短暂接触糖皮质激素(GC)可增强体能并提高 忍耐力。矛盾的是，尽管有这些提高性能的好处，但GC并不是常规的 开给非炎症性疾病的处方，因为标准的每日GC剂量方案导致明显 肌肉萎缩。在这笔尖顶拨款中，我们将检验每周一次类固醇给药的假设 在肌肉萎缩模型中，改善肌肉功能和生长。肌肉萎缩将在 通过石膏固定小鼠，因为长时间的石膏浇铸是导致退伍军人萎缩的常见事件 而且不会破坏神经血管结构。实验设计为双因素方差分析模型。 共7组小鼠，随机分为雄性和雌性小鼠各6只 每组)。小鼠在铸造过程中给予0.1 mg/kg或1 mg/kg的泼尼松类固醇 铸造(回收)或在铸造和回收期间两者兼而有之。PBS的“剂量”将被用作对照。 肌力产生、基因表达、大小、耐力能力和肌肉质量 这些治疗中的每一种。从这笔尖顶拨款产生的数据将使人类能够设计出 在退伍军人群体中改进这些治疗方法的研究。

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.