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

这个项目的目的是阐明长期的包括延长和缩短肌肉收缩的体育训练是如何增加人类肌肉的大小和力量的，而不仅仅是缩短收缩，以及慢性摄入非甾体抗炎药是否会损害这一过程。在与英国体育的合作中，BBSRC为研究应用提供了资金，这些研究应用将专门利用“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”，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要求：(i)尽管我们知道，与只进行缩短肌肉收缩的训练相比，结合延长和缩短肌肉收缩的阻力训练能获得更大的肌肉质量和力量增长，并且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，我们对这种类型的训练中肌肉性能提高和生理变化的时间过程一无所知。众所周知，与缩短收缩相比，单次延长收缩后肌肉炎症更严重，这可能是重要的。因此，我们的目标是使用基本的生物科学方法来检查增强的肌肉生长因子表达和肌肉特异性干细胞增殖，我们认为这是运动诱导的肌肉炎症的继发发生，是否是持续的训练包括延长和缩短收缩的联合训练比只包括缩短收缩的训练增加肌肉质量和力量增益的机制。这方面的项目将提供详细的，广泛的机制洞察阻力运动训练如何导致积极的肌肉适应和人类的功能增益。除了对我们对运动压力的生理适应的基本理解具有重要意义，从而最大限度地提高运动成绩，它还与我们对如何最大限度地减少伴随衰老而来的肌肉质量损失（肌肉萎缩症）的理解具有更广泛的相关性。（ii）非甾体抗炎药（NSAID’s）在顶级运动中被广泛用作预防药物，似乎可以最大限度地减少疼痛和损伤，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）中的新作用，长期预防性使用NSAID很可能会损害肌肉对阻力训练的适应能力。从而削弱运动员的表现发展（除了不安全）。目前的项目将解决英国高性能运动面临的一个主要挑战，即确定在抗阻训练计划中摄入非甾体抗炎药是否会减弱训练引起的肌肉功能的增加（通过减轻肌肉炎症、肌肉生长因子反应和干细胞激活和增殖）。显然，这个项目将为运动员预防性使用非甾体抗炎药的潜在负面影响提供有价值的、新颖的信息，从而满足英国体育将基础生物学研究与高水平运动联系起来的要求。

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.