The effects of muscular dystrophy, exercise and sActRIIB-Fc on molecular signature of skeletal muscle in mice

To study the combined effect of myostatin/activin inhibition and exercise on muscle mass and pathophysiology, young mdx mice, a model for Duchenne Muscular Dystrophy, were injected with soluble activin receptor-Fc (sActRIIB-Fc) or placebo (PBS) 1x/week for a 7-week period, in combination with or without voluntary running. C57Bl/10ScSnJ mice injected with PBS acted as wildtype controls. Microarray expression analysis from skeletal muscle was performed using m. gastrocnemies as the sample. We found thatexercise or a combination of exercise and sActRIIB-Fc treatment is more effective in correcting gene expression profiles of dystrophic muscles than the sActRIIB-Fc treatment alone. We also identified several pathways and proteins that were affected by exercise and sActRIIB-Fc together or independently. Total RNA obtained from gastrocnemius muscle of mdx mice divided into four groups: 1) control (injected with PBS, n=5), 2) runners (voluntary wheel running for 7 weeks, injected with PBS, n=5), 3) sActRIIB-Fc -treated (n=5), and 4) runners with sActRIIB-Fc-treatment (n=5). sActRIIB-Fc or PBS was injected intraperitoneally once a week with a 5-mg/kg dose of sActRIIB-Fc. In addition, wildtype mice served as healthy controls (n=4).

为探究肌抑素/激活素抑制联合运动对肌肉质量与病理生理过程的联合效应，本研究以杜氏肌营养不良症（Duchenne Muscular Dystrophy）模型幼龄mdx小鼠为实验对象，每周1次给予可溶性激活素受体-Fc（soluble activin receptor-Fc，缩写sActRIIB-Fc）或安慰剂（PBS，即磷酸盐缓冲液），干预周期为7周，同时设置自愿跑轮运动或无运动的对照条件。以注射PBS的C57Bl/10ScSnJ小鼠作为野生型对照。本研究以腓肠肌（gastrocnemius）为样本，对骨骼肌组织开展微阵列基因表达分析。研究结果显示，相较于单独使用sActRIIB-Fc治疗，运动或运动联合sActRIIB-Fc治疗在纠正营养不良性肌肉的基因表达谱方面效果更为显著。此外，本研究还鉴定出若干分别或共同受运动与sActRIIB-Fc调控的信号通路及蛋白质。本研究从mdx小鼠的腓肠肌中提取总RNA，将实验样本分为4组：1）空白对照组（注射PBS，n=5）；2）运动对照组（接受7周自愿跑轮运动，同时注射PBS，n=5）；3）sActRIIB-Fc单药治疗组（n=5）；4）运动联合sActRIIB-Fc治疗组（n=5）。sActRIIB-Fc与PBS均采用每周1次腹腔注射的给药方式，其中sActRIIB-Fc的给药剂量为5 mg/kg。此外，野生型小鼠作为健康对照（n=4）。