Vanderbilt University, Nashville, Tennessee, and Karolinska Institutet and Karolinska University Hospital, Solna, Stockholm, Sweden.
Karolinska Institutet and Karolinska University Hospital, Solna, Stockholm, Sweden.
Arthritis Rheumatol. 2016 Jul;68(7):1738-50. doi: 10.1002/art.39624.
Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM.
Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12-week follow-up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry-based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise.
Compared to the control group, the exercise group improved in minutes of cycling time (P < 0.01) and Vo2 max (P < 0.05). The exercise group also had reduced disease activity (P < 0.05) and reduced lactate levels at exhaustion (P < 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up-regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down-regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm(2) in follow-up biopsy samples (P < 0.05).
Our data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients' muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies.
耐力运动对多发性肌炎/皮肌炎（PM/DM）有益；然而，运动对骨骼肌的分子影响尚未完全了解。我们进行了这项对照性初步研究，以调查与未运动的 PM/DM 患者对照组相比，为期 12 周的耐力运动训练计划对已确诊 PM/DM 患者骨骼肌分子特征的影响。
纳入了 15 名（运动组 7 名，对照组 8 名）有配对基线和 12 周随访肌肉活检样本的患者。对肌肉活检样本进行信使 RNA 表达谱分析、基于质谱的定量蛋白质组学和免疫组织化学分析，以确定与耐力运动引起的临床测量变化相关的分子适应性。
与对照组相比，运动组在骑自行车时间（P < 0.01）和 Vo2 max（P < 0.05）方面均有改善。运动组的疾病活动度也降低（P < 0.05），运动后疲劳时的乳酸水平降低（P < 0.05）。与毛细血管生长、线粒体生物发生、蛋白质合成、细胞骨架重塑和肌肉肥大相关的基因在运动组上调，而与炎症/免疫反应和内质网应激相关的基因下调。蛋白质组学分析表明，与耐力运动相关的基因主要涉及线粒体途径，包括氧化磷酸化代谢途径。运动组在随访活检样本中也显示出更高的每平方毫米毛细血管数（P < 0.05）。
我们的数据表明，患有确诊的 PM 和 DM 的患者进行耐力运动可能会激活有氧表型并促进肌肉生长，同时抑制这些患者肌肉中的炎症反应，这得到了重复肌肉活检中的基因表达、蛋白质组学和毛细血管密度数据的支持。
