Mechanisms underlying local and systemic effects of massage

按摩局部和全身效应的机制

• 批准号: 10055850
• 负责人: Timothy Alan Butterfield
• 金额: $ 24.28万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10055850
• 关键词: Acquired Immunodeficiency Syndrome; Address; Aging; Anabolism; Anxiety; Area; Atrophic; Attenuated; Biogenesis; Biopsy; Brain; Cell Count; Cell physiology; Cells; Clinical; Communication; Complementary Health; Congestive Heart Failure; Contralateral; DNA; DNA biosynthesis; Data; Devices; Diabetes Mellitus; Disease; Distant; Disuse Atrophy; Female; Funding Opportunities; Future; Goals; Grant; Health; Health Benefit; Human; Immunity; Integrative Medicine; Intensive Care Units; Intervention; Limb structure; Lipids; Lower Extremity; Maintenance; Malignant Neoplasms; Massage; Measurement; Measures; Mechanical Stimulation; Mechanics; Mediator of activation protein; Membrane Lipids; Mental Depression; MicroRNAs; Mind-Body Intervention; Muscle; Muscle Fibers; Muscle Proteins; Muscular Atrophy; NIH Program Announcements; Neurons; Organ; Orthopedic Surgery procedures; Outcome; Participant; Pathway interactions; Patients; Population; Process; Protein Biosynthesis; Proteins; Quality of life; RNA; Rattus; Regulation; Research; Resistance; Ribosomes; Science; Sedation procedure; Serum; Serum Markers; Site; Skeletal Muscle; Suspensions; Testing; Tissues; Trauma; associated symptom; attenuation; clinically significant; common symptom; extracellular vesicles; human subject; innovation; male; mechanical load; mechanotransduction; muscle form; novel; outcome forecast; pain relief; primary outcome; protein degradation; release factor; resistance exercise; response; satellite cell; secondary outcome; skeletal muscle wasting; standard care; symptom management; vesicular release; young adult

SUMMARY The loss of skeletal muscle mass is a common symptom associated with diseases such as cancer, AIDS, diabetes, congestive heart failure, and with aging. Muscle atrophy is associated with poor disease prognosis and decreased quality of life and therefore, maintaining muscle size and reducing the loss of muscle during disuse atrophy is of vital significance. Mechanical stimulation of muscle, such as during resistance exercise, induces protein synthesis needed to increase muscle protein content and muscle size. We showed that mechanical stimulation applied to skeletal muscle in the form of massage is an effective mechanotherapy in rats, since it leads to a shift in protein turnover favoring anabolism and enhanced regrowth after disuse-induced atrophy. Whether the same positive effect of massage occurs in humans is currently unknown, but would be extremely beneficial for skeletal muscle and overall health in case where resistance exercise is contraindicated or not feasible. In addition to the direct anabolic effects on the massaged rat muscle, we showed an equally beneficial response on the homologous muscle in the contralateral non-massaged limb of rats and humans. This novel finding indicated the existence of indirect mechanisms that could have profound systemic effects beyond the massaged muscle. Extracellular vesicles (EVs) are lipid membrane-bound vesicles released from cells with the ability to modulate function of cells from which they are released, as well as in cells with which they fuse. As such EVs are likely mediators of the well-documented but poorly-understood effects of massage in humans on the brain and other organs, such as relief of pain, anxiety or depression or changes in immunity. Therefore, the goal of this proposal is to determine anabolic effects of massage in human muscle, and to identify whether EVs released with massage are candidates for beneficial effects of this mechanotherapy on muscle as well as other organs. The contribution of neuronal activity will also be investigated. In Aim 1 we will address the following hypothesis: Massage acts as a mechanotherapy by shifting protein biogenesis towards anabolism. Using a novel massage device we will apply mechanical load to muscle undergoing atrophy through unilateral lower limb suspension and mechanisms underlying muscle size regulation determined. Protein synthesis will be the primary outcome. In the exploratory Aim 2 we will test the hypothesis that massage induces cross-over effects through changes in EVs or neuronal activity. We will measure EVs and their miRNA cargo in the serum, and markers of EV biogenesis in muscle of human subjects from Aim 1. Muscle activation in the contralateral limb will also be measured. Results from this study will indicate not only how mechanotherapy, such as massage, can attenuate atrophy and enhance anabolic processes during disuse, but also determine whether EVs are a candidate mechanism for the overall health benefits of massage. This application directly addresses the goals set out in the following program announcement from the National Center for Complementary and Integrative Health: PA-18-322 Health: Fundamental Science Research on Mind and Body Approaches (R21).

摘要 骨骼肌块的减少是癌症、艾滋病、糖尿病、充血性心力衰竭和衰老等疾病的常见症状。肌肉萎缩与疾病预后不良和生活质量下降有关，因此，在废用性萎缩期间保持肌肉大小并减少肌肉损失具有重要意义。机械刺激肌肉，如在阻力运动中，诱导蛋白质合成，以增加肌肉蛋白质含量和肌肉大小。我们证明，以按摩的形式对骨骼肌进行机械刺激是一种有效的机械疗法，因为它导致蛋白质周转转变，有利于合成代谢，并在废用诱导的萎缩后促进再生。目前尚不清楚按摩是否会在人类身上产生同样的积极效果，但如果阻力运动是禁忌或不可行的，那么对骨骼肌和整体健康将是极其有益的。除了对接受按摩的大鼠肌肉有直接的合成代谢作用外，我们还在大鼠和人类的对侧非按摩肢体的同种肌肉上显示了同样有益的反应。这一新的发现表明，间接机制的存在可能会对按摩肌肉以外的系统产生深远的影响。细胞外小泡(EVS)是从细胞释放的脂膜结合的囊泡，具有调节释放细胞和融合细胞的功能的能力。因此，电动汽车可能是人类按摩对大脑和其他器官的影响(如缓解疼痛、焦虑或抑郁或免疫力变化)的媒介，这些影响有很好的记录，但知之甚少。因此，这项建议的目标是确定按摩对人体肌肉的合成代谢影响，并确定随按摩释放的电动汽车是否适合这种机械疗法对肌肉和其他器官的有益影响。神经元活动的贡献也将被调查。在目标1中，我们将解决以下假设：按摩作为一种机械疗法，通过将蛋白质生物发生转变为合成代谢来发挥作用。使用一种新的按摩器，我们将通过单侧下肢悬吊对正在萎缩的肌肉施加机械载荷，并确定肌肉大小调节的机制。蛋白质合成将是主要结果。在探索性目标2中，我们将检验这样一种假设，即按摩通过EVS或神经元活动的变化来诱导交叉效应。我们将从Aim 1开始测量血清中EV及其miRNA载量，以及EV生物发生的人体肌肉标志物。还将测量对侧肢体的肌肉激活。这项研究的结果将不仅表明机械疗法，如按摩，如何在停用期间减轻萎缩和增强合成代谢过程，而且还将确定电动汽车是否为按摩总体健康益处的候选机制。这项申请直接解决了国家补充和综合健康中心的以下计划公告中提出的目标：PA-18-322健康：关于心理和身体方法的基础科学研究(R21)。