COX Inhibition & Musculoskeletal Responses to Exercise

COX抑制

基本信息

批准号：
7475153
负责人：
Wendy M Kohrt
金额：
$ 55.55万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-05-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7475153
关键词：
Acids Address Aging Animals Anti-Inflammatory Agents Anti-inflammatory Area Attenuated Award Biological Bone Density Bone Formation Inhibition Bone Resorption Bone Resorption Stimulation Chronic Conflict (Psychology)Cyclooxygenase Inhibitors Data Dinoprostone Drug Exposure Drug usage Effectiveness Elderly Enzymes Epidemiologic Studies Exercise Fatty acid glycerol esters Figs - dietary Gene Expression Genes Hip region structure Human Ibuprofen Inflammation Intervention Studies Knowledge Learning Left Measures Mechanical Stimulation Mechanical Stress Mechanics Mediating Metabolic Muscle Muscle Proteins Muscle function Musculoskeletal Nature Observational Study Osteoblasts Osteogenesis Osteoporosis Outcome Participant Pathway interactions Performance Pharmaceutical Preparations Phosphorylation Physical Function Placebos Play Population Prevention Prospective Studies Prostaglandin Production Prostaglandin-Endoperoxide Synthase Prostaglandins Prostaglandins E Protein Biosynthesis Proteolysis Publishing Randomized Randomized Controlled Trials Rate Rattus Recruitment Activity Relative (related person)Reporting Research Personnel Resistance Risk Role ST5 Protein ST5 gene Signal Pathway Skeletal Muscle Skeletal bone Skeletal system Stress Time Tissues Title Training Training Programs Upper arm Vertebral column Weight Lifting Weight-Bearing state Woman age related aged bone bone metabolism bone preservation bone turnover clinically significant cyclooxygenase 1 cyclooxygenase 2 dehydroepiandrosterone disability frailty hip bone human FRAP1 protein ilium improved insight interest men muscle hypertrophy muscle metabolism muscle strength myogenesis older women programs protein metabolism response sarcopenia substantia spongiosa

项目摘要

DESCRIPTION (provided by applicant): This is a competing continuation application of the project entitled Biological Effects of DHEA in the Elderly. As noted by the new title, COX Inhibition & Musculoskeletal Responses to Exercise, the application is a continuation of the study of factors that influence bone and muscle metabolism in aging. There is compelling evidence from studies of animals that prostaglandins (PG) are important factors in the bone formation and muscle protein synthesis responses to mechanical stress (i.e., exercise) and that cyclooxygenase (COX) is a key enzyme for mechanically-induced PG synthesis. Inhibition of COX activity, via non-steroidal anti- inflammatory drugs (NSAIDs), has been found to markedly blunt the osteogenic and myogenic responses to mechanical stress. There have been no prospective studies in humans of the potential effects of NSAIDs to impair the anabolic actions of exercise on bone and muscle. Accordingly, the global aim for the next award period is to determine whether use of ibuprofen before, but not after, exercise attenuates the anabolic effects of exercise training on bone and skeletal muscle in older women and men. To address this aim, women and men (n=150), aged 60-75 yr, will be recruited to participate in 9 months of supervised exercise training. The exercise program will be progressive in nature and include high-intensity weight lifting and weight-bearing exercises to stimulate increases in bone mineral density (BMD) and fat-free mass (FFM). Participants will be randomized to three treatment arms: ibuprofen 400 mg before exercise and placebo after (n=50), placebo before exercise and ibuprofen 400 mg after (n=50), and placebo before and after exercise (n=50). It is hypothesized that increases in lumbar spine BMD, total hip BMD, and fat-free mass (FFM) in response to 9 months of exercise training will be significantly less in women and men taking ibuprofen before exercise than in those taking ibuprofen after exercise or placebo. The importance of this study centers on the knowledge that declining levels of BMD and FFM are harbingers of osteoporosis, sarcopenia, and physical frailty in aging. High-intensity exercise that has the potential to improve BMD, muscle mass, strength, and physical function has become the cornerstone for the prevention and treatment of age-related physical disability. Therefore, knowledge of whether a drug as widely used as ibuprofen impairs the beneficial adaptations to exercise is deemed to be of high clinical significance.

描述（由申请人提供）：这是该项目的竞争性延续应用，名为DHEA在老年人中的生物学作用。正如新标题所指出的，Cox抑制和肌肉骨骼对运动的反应是，应用是对影响衰老中骨骼和肌肉代谢的因素的延续。从对动物的研究中有令人信服的证据表明，前列腺素（PG）是骨形成和肌肉蛋白合成对机械胁迫（即运动）的重要因素，并且环氧酶（COX）是机械诱导的PG合成的关键酶。通过非甾体抗炎性药物（NSAID）抑制COX活性明显钝化了成骨和肌源性对机械应激的反应。在人类中，没有关于NSAID的潜在影响损害运动代谢作用对骨骼和肌肉的作用的前瞻性研究。因此，下一个奖励期的全球目标是确定以前但不以前的布洛芬的使用是否会减弱运动训练对老年男女骨骼和骨骼肌的合成代谢作用。为了解决这一目标，将招募60 - 75岁的男女（n = 150）参加9个月的监督运动培训。运动计划本质上是渐进的，包括高强度举重和体重锻炼，以刺激骨矿物质密度（BMD）和无脂肪质量（FFM）的增加。参与者将被随机分为三个治疗臂：锻炼前400毫克布洛芬（n = 50），锻炼前安慰剂和安慰剂，在运动前和布洛芬400毫克（n = 50）和安慰剂前后运动前和安慰剂（n = 50）。假设腰椎BMD，总髋关节BMD和无脂肪质量（FFM）的增加，对9个月的运动训练的响应在运动前接受布洛芬的男性和男性在运动前的运动训练的幅度要小于运动或安慰剂后接受布洛芬或安慰剂后。这项研究的重要性集中在BMD和FFM水平下降的知识中，这是骨质疏松症，肌肉减少症和衰老中的身体脆弱者的预兆。具有改善BMD，肌肉质量，力量和身体机能的潜力的高强度运动已成为预防和治疗与年龄相关的身体残疾的基石。因此，了解像布洛芬一样广泛使用的药物会损害运动的有益适应性是否具有很高的临床意义。