ACETAMINOPHEN AND IMPAIRED MUSCULOSKELETAL ADAPTATIONS TO EXERCISE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 机械压力(例如，锻炼)会导致骨骼肌和骨骼中前列腺素(PGs)的增加。PG由环氧合酶(COX)激活。动物研究表明，PGs的增加对骨形成至关重要。当COX活性被非类固醇抗炎药(NSAIDs)抑制时，如布洛芬(IBUP)，骨形成反应几乎完全消除。对乙酰氨基酚(ACET)是一种止痛剂，在某些组织中也可能抑制COX活性。如果这发生在人类肌肉和骨骼中，这些组织中的机械信号可能会因ACET的使用而受损。解决这一问题的唯一研究发现，IBUP和ACET都钝化了一轮阻力运动后人体骨骼肌PG的增加，同时伴随着肌肉蛋白质积累的钝化增加。目前尚不清楚ACET和IBUP在一次运动中对肌肉PG和蛋白质的影响是否持续到重复运动(即运动训练)，或者ACET和IBUP是否通过类似的细胞机制发挥作用。ACET是否会损害骨组织对机械负荷的反应也是未知的。因此，拟议研究的主要目的是确定ACET对肌肉和骨骼对运动训练的适应性的影响，并评估ACET影响肌肉代谢的潜在机制；将纳入IBUP手臂，以深入了解ACET和IBUP是否通过类似的机制发挥作用。男性(n=31)，60岁以上，将接受为期4个月的监督运动训练，其中包括高强度举重和负重运动，以刺激肌肉和骨骼的形成。参与者将被随机分为ACET(1000 mg/d；n=12)、IBUP(400 mg/d；n=7)或PLAC(n=12)。我们假设，与PLAC相比，使用ACET会减少肌肉质量和骨形成标记物(在血液中发现)的增加。我们进一步假设，与运动+ACET或+IBUP相比，信号肌肉形成的分子对运动+PLAC的反应方向不同。这项研究的重要性集中在老年人中广泛使用止痛药，这是一个肌肉和骨量丧失风险增加的人群，以及身体损伤。尽管高强度运动有可能改善老年人的肌肉质量、力量、身体功能和骨密度，但ACET的使用可能通过干扰肌肉和骨细胞中的分子信号来损害这些适应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mechanical stress (e.g., exercise) triggers an increase in substances known as prostaglandins (PGs) in skeletal muscle and bone. PGs are activated by the enzyme cyclooxygenase (COX). Animal studies show that an increase in PGs is essential for bone formation. When COX activity is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (IBUP), the bone formation response is almost completely eliminated. Acetaminophen (ACET) is an analgesic that may also inhibit COX activity in some tissues. If this occurs in human muscle and bone, it is possible that mechanical signaling in these tissues would be impaired by ACET use. The only study to address this found that both IBUP and ACET blunted the increase in PGs after one bout of resistance exercise in human skeletal muscle, and this was accompanied by a blunted increase in muscle protein build-up. It is not known whether the observed effects of ACET and IBUP on muscle PGs and protein in response to one bout of exercise persist with repeated bouts of exercise (i.e., exercise training), or whether ACET and IBUP act through similar cellular mechanisms. It is also unknown whether ACET impairs the bone building responses to mechanical loading. Accordingly, the primary aims of the proposed studies are to determine the effects of ACET on the muscle and bone adaptations to exercise training and to evaluate potential mechanisms by which ACET influence muscle metabolism; an IBUP arm will be included to gain insight into whether ACET and IBUP act through similar mechanisms. Men (n=31), aged 60 yr+, will undergo 4 months of supervised exercise training that will include high-intensity weight lifting and weight-bearing exercises to stimulate muscle and bone building. Participants will be randomized to ACET (1000 mg/d; n=12), IBUP (400 mg/d; n=7), or PLAC (n=12). We hypothesize that increases in muscle mass and bone formation markers (found in blood) will be reduced by the use of ACET compared with PLAC. We further hypothesize that molecules that signal muscle building will respond in different directions to exercise + PLAC when compared with exercise + ACET or + IBUP. The importance of this study centers on the widespread use of analgesics among the elderly, a population at increased risk for loss of muscle and bone mass, and physical impairment. Although high-intensity exercise has the potential to improve muscle mass, strength, physical function, and bone mineral density in the elderly, it is possible that the use of ACET impairs these adaptations by interfering with molecular signals in muscle and bone cells.