Department of Neuroscience Imaging and Clinical Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Interuniversity Institute of Myology, Italy.
J Appl Physiol (1985). 2017 Sep 1;123(3):501-512. doi: 10.1152/japplphysiol.00855.2016. Epub 2017 Jun 1.
The aim of this study was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 wk of NMES were allowed to proliferate to provide myogenic populations of adult stem cells [myogenic precursor cells (MPCs)]. These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca concentrations, and their expression of myogenic regulatory factors (, and ) and micro-RNAs (miR-1, miR-133a/b, and miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross-sectional area, and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca concentrations and gene expression of and on MPCs. Muscle-specific miR-1, miR-133a/b, and miR-206 were upregulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cell fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly subjects significantly improved. NMES may thus be further considered for clinical or ageing populations. The neuromuscular electrical stimulation (NMES) effect on skeletal muscle regeneration was assessed in healthy elderly subjects for the first time. NMES improved the regenerative capacity of skeletal muscle through increased myogenic precursor cell proliferation and fusion with mature myofibers. The increased cytoplasmic free Ca concentration along with , , and micro-RNA upregulation could be related to reduced O production, which, in turn, favors myogenic regeneration. Accordingly, the skeletal muscle strength of NMES-stimulated lower limbs of healthy elderly subjects improved along with their mobility.
本研究旨在确定神经肌肉电刺激（NMES）是否通过降低健康老年受试者卫星细胞的氧化状态来影响骨骼肌再生。在 NMES 治疗 8 周前后，取自 12 名健康老年受试者股外侧肌的卫星细胞被允许增殖，以提供成体干细胞的肌源性群体[成肌前体细胞（MPCs）]。然后，这些 MPCs 的增殖能力、基础细胞质游离 Ca 浓度、肌生成调节因子（、和）和 microRNA（miR-1、miR-133a/b 和 miR-206）的表达情况进行了研究。通过超氧阴离子产生和超氧化物歧化酶及谷胱甘肽过氧化物酶活性来评估这些 MPC 的氧化状态。在分离的单个骨骼肌纤维上，计数细胞核以确定肌核密度、纤维表型、横截面积和产生的张力。NMES 后获得的 MPCs 显示增殖率增加，同时细胞质游离 Ca 浓度增加，MPCs 中的基因表达增加。肌肉特异性 miR-1、miR-133a/b 和 miR-206 上调。NMES 显著降低超氧阴离子的产生，同时超氧化物歧化酶活性呈下降趋势。NMES 依赖性的肌肉再生刺激增强了卫星细胞与成熟骨骼肌纤维的融合。NMES 改善了老年受试者的骨骼肌再生能力。因此，NMES 刺激的老年受试者的骨骼肌力量和活动能力显著提高。NMES 因此可能进一步被考虑用于临床或老龄化人群。这是首次在健康老年受试者中评估神经肌肉电刺激（NMES）对骨骼肌再生的影响。NMES 通过增加成肌前体细胞的增殖和与成熟肌纤维的融合来改善骨骼肌的再生能力。细胞质游离 Ca 浓度的增加以及、和 microRNA 的上调可能与减少 O 的产生有关，而 O 的产生反过来又有利于肌生成的再生。因此，NMES 刺激的健康老年受试者下肢的骨骼肌力量提高，同时活动能力也提高。
