Bass Joseph J, Hardy Edward J O, Inns Thomas B, Wilkinson Daniel J, Piasecki Mathew, Morris Robert H, Spicer Abi, Sale Craig, Smith Ken, Atherton Philip J, Phillips Bethan E
MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), University of Nottingham, Nottingham, United Kingdom.
Department of Surgery and Anaesthetics, Royal Derby Hospital, Derby, United Kingdom.
Front Physiol. 2021 May 4;12:653060. doi: 10.3389/fphys.2021.653060. eCollection 2021.
Disuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant (TA) and Atrophy Susceptible (MG) muscles (aRaS) with a future view of uncovering central mechanisms.
Seven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted.
TA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (-2.8 ± 1.4%, < 0.05) and muscle thickness decreased (-12.9 ± 1.6%, < 0.01), with a positive correlation between changes in muscle volume and thickness (R = 0.31, = 0.038). Importantly, both TA muscle volume and thickness remained unchanged.
The use of this unique "aRaS" paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA.
废用性萎缩(DA)是指因不活动引起的骨骼肌丢失,其机制尚未完全明确。一个有趣的现象是,尽管各肌肉具有相似的解剖功能/位置,但它们表现出不同程度的萎缩。我们旨在开发一种创新的实验范式,以研究抗萎缩(TA)和易萎缩(MG)肌肉(aRaS)[注1],以期揭示其中的核心机制。
7名健康青年男性(22±1岁)接受了15天的单侧腿部固定(ULI)。参与者使用膝关节支具和空气靴将单腿固定(膝关节屈曲75°),脚踝也固定到位。在固定期前后,对小腿进行双能X线吸收法(DXA)、MRI和超声扫描,以确定肌肉质量的变化。开发了用于在固定后(双侧肢体)对TA/MG肌肉进行鼻甲刀和微针活检的技术,并进行了初步的纤维类型分析。
TA/MG肌肉显示出相当的纤维类型分布,主要为I型纤维(TA为67±7%[注2],MG为63±5%)。固定15天后,MG肌肉体积(-2.8±1.4%,P<0.05)和肌肉厚度下降(-12.9±1.6%,P<0.01),肌肉体积和厚度的变化之间存在正相关(R = 0.31,P = 0.038)。重要的是,TA肌肉体积和厚度均保持不变。
使用这种独特的“aRaS”范式为研究人类不同DA易感性的机制基础提供了一种有效且便捷的方法,这可能有助于获得新的机制见解,并进而减轻人类DA期间的骨骼肌萎缩。
注1:这里的aRaS是作者自己定义的一种概念,在文中首次出现,直接保留英文缩写。
注2:这里的±表示标准差,在中文中直接保留英文符号。