Mechanism of eccentric training augmentation of muscle adaptation in humans and the potential negative impact of non-steroidal anti-inflammatory drugs

离心训练增强人类肌肉适应的机制以及非甾体抗炎药的潜在负面影响

• 批准号: BB/I020713/1
• 负责人: Paul Greenhaff
• 金额: $ 48万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI020713%2F1
• 关键词: Mechanism; eccentric; training; augmentation; muscle

This project is aimed at elucidating how long-term physical training involving both lengthening and shortening muscle contractions increases muscle size and strength in humans above shortening contractions alone, and whether chronic ingestion of non-steroidal anti-inflammatory drugs impairs this process. In collaboration with UK Sport, the BBSRC has made funding available for research applications that will specifically utilise 'fundamental bioscience to provide new insights into the stress and adaptation required to maximise physical potential', and by doing so will 'address many of the major challenges facing high performance sport in the UK through athletic training and performance.' This project meets this remit on two fronts: (i) Although we know that resistance training which involves a combination of lengthening and shortening muscle contractions results in greater muscle mass and strength gains than training involving only shortening contractions, and is used widely by athletes to maximise performance gains, our understanding of the mechanisms by which this is achieved is at a rudimentary level. Furthermore, we know nothing about the time-course of muscle performance gains and physiological changes that occur during this type of training. It is known that muscle inflammation is greater after a single bout of lengthening contractions compared to shortening contractions, which may be important. Therefore we aim to use a basic bioscience approach to examine whether augmented muscle growth factor expression and muscle specific stem cell proliferation, that we believe occur secondary to exercise induced muscle inflammation, is the mechanism by which a sustained period of training involving combined lengthening and shortening contractions augments muscle mass and strength gains over training involving only shortening contractions. This aspect of the project will provide detailed, broad-based mechanistic insight of how resistance exercise training results in positive muscle adaptation and functional gains in humans. In addition to being of importance to our fundamental understanding of physiological adaptation to exercise stress, and thereby maximising athletic performance, it has wider relevance to our understanding of how we might minimise the loss of muscle mass that accompanies ageing (sarcopaenia). (ii) Non-steroidal anti-inflammatory drugs (NSAID's) are widely used in top level sport as a prophylactic agent to seemingly minimise pain and injury and maximise training adaptation, but given the emerging role of inflammation in stimulating muscle growth responses (including muscle stem cell activation), there is a distinct possibility that chronic prophylactic use of NSAID's may impair muscle adaptation to resistance training, thereby blunting athlete performance development (in addition to being unsafe). The present project will address a major challenge facing high performance sport in the UK by determining whether NSAID ingestion during a programme of resistance training can blunt training induced increases in muscle function (by attenuating muscle inflammation, muscle growth factor responses and stem cell activation and proliferation). Clearly therefore this project will provide valuable, novel information concerning the potential negative effect of prophylactic NSAID use by athletes, thereby fulfilling the requirement of UK Sport of linking fundamental biological research to high performance sport.

这个项目的目的是阐明长期的体育锻炼，包括延长和缩短肌肉收缩，如何在人类中增加肌肉的大小和力量，而不仅仅是缩短收缩，以及长期摄入非类固醇抗炎药是否会损害这一过程。BBSRC与英国体育中心合作，为研究应用提供了资金，这些应用将专门利用基础生物科学为最大限度地发挥身体潜力所需的压力和适应提供新的见解，通过这样做，将通过运动训练和表现解决英国高性能运动面临的许多主要挑战。该项目在两个方面满足了这一任务：(I)尽管我们知道，与只进行缩短收缩的训练相比，结合了延长和缩短肌肉收缩的阻力训练可以产生更大的肌肉质量和力量增长，并被运动员广泛用于最大限度地提高成绩，但我们对实现这一目标的机制的理解还处于初级水平。此外，我们对这类训练中肌肉性能增长的时间进程和发生的生理变化一无所知。众所周知，与缩短收缩相比，单次延长收缩后的肌肉炎症更严重，这可能是重要的。因此，我们的目标是使用一种基本的生物科学方法来检验肌肉生长因子表达增强和肌肉特异性干细胞增殖是否是持续训练的机制，通过这种机制，持续的训练包括延长和缩短收缩，从而增加肌肉质量和力量增长，而不是只进行缩短收缩的训练。我们认为，肌肉生长因子表达增强和肌肉特异性干细胞增殖是运动引起肌肉炎症的继发因素。该项目的这一方面将提供关于阻力运动训练如何在人类中产生积极的肌肉适应和功能获得的详细的、基础广泛的机械学见解。除了对我们对运动压力的生理适应的基本理解非常重要，从而使运动表现最大化之外，它还与我们对如何最大限度地减少随年龄增长而损失的肌肉质量(石棺减少)的理解有更广泛的相关性。(Ii)非类固醇抗炎药(NSAID)在顶级运动中被广泛用作预防性药物，似乎可以最大限度地减少疼痛和伤害，并最大限度地提高训练适应能力，但鉴于炎症在刺激肌肉生长反应(包括肌肉干细胞激活)方面的新作用，长期预防性使用NSAID很可能会损害肌肉对阻力训练的适应，从而削弱运动员的成绩发展(除了不安全外)。本项目将解决英国高性能运动面临的一个主要挑战，通过确定在阻力训练计划中摄入非甾体抗炎药是否可以钝化训练引起的肌肉功能增加(通过减轻肌肉炎症、肌肉生长因子反应以及干细胞激活和增殖)。因此，该项目显然将提供有关运动员预防性使用非甾体抗炎药的潜在负面影响的有价值的新信息，从而满足英国体育将基础生物学研究与高性能运动联系起来的要求。

项目成果

Chronic NSAID ingestion augments muscle cross-sectional area and volume during resistance exercise training in young men

长期摄入非甾体抗炎药会增加年轻男性阻力运动训练期间的肌肉横截面积和体积

• 发表时间: 2014
• 作者: Mallinson JA

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.

年龄和单侧腿部固定 2 周对人体骨骼肌中等强度运动期间基质利用率的影响。

• DOI: 10.1113/jp271712
• 发表时间: 2016
• 期刊: The Journal of physiology
• 作者: Vigelsø A

Longitudinal hypertrophic and transcriptional responses to high-load eccentric-concentric vs concentric training in males.

男性对高负荷偏心-向心与向心训练的纵向肥大和转录反应。

• DOI: 10.1111/sms.13791
• 发表时间: 2020
• 期刊: Scandinavian journal of medicine & science in sports
• 影响因子: 4.1
• 作者: Mallinson JE

Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis, Breakdown, and Insulin Resistance-A Qualitative Review.

• DOI: 10.3389/fphys.2016.00361
• 发表时间: 2016
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Rudrappa SS;Wilkinson DJ;Greenhaff PL;Smith K;Idris I;Atherton PJ
• 通讯作者: Atherton PJ

Statin myalgia does not reduce muscle strength, mass or protein turnover, but is associated with impaired dynamic muscle function and insulin resistance in older male volunteers

他汀类药物肌痛不会降低肌肉力量、质量或蛋白质周转率，但与老年男性志愿者的动态肌肉功能受损和胰岛素抵抗有关

• 发表时间: 2013
• 作者: Mallinson J