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).

概括 骨骼肌质量损失是与癌症、艾滋病、糖尿病、充血性心力衰竭和衰老等疾病相关的常见症状。肌肉萎缩与疾病预后不良和生活质量下降有关，因此，维持肌肉大小并减少废用性萎缩期间的肌肉损失至关重要。对肌肉的机械刺激（例如在抗阻运动期间）会诱导增加肌肉蛋白质含量和肌肉大小所需的蛋白质合成。我们证明，以按摩的形式施加于骨骼肌的机械刺激是对大鼠的一种有效的机械疗法，因为它会导致蛋白质周转发生有利于合成代谢的转变，并在废用引起的萎缩后增强再生。目前尚不清楚按摩是否会对人类产生同样的积极作用，但在阻力运动禁忌或不可行的情况下，这对骨骼肌和整体健康极其有益。除了对按摩的大鼠肌肉的直接合成代谢作用外，我们还对大鼠和人类对侧未按摩肢体的同源肌肉显示出同样有益的反应。这一新发现表明间接机制的存在可能对按摩肌肉产生深远的系统影响。细胞外囊泡 (EV) 是从细胞中释放的脂质膜结合囊泡，能够调节释放它们的细胞以及与其融合的细胞的功能。因此，电动汽车可能是按摩对人类大脑和其他器官产生的有据可查但知之甚少的影响的中介者，例如缓解疼痛、焦虑或抑郁或改变免疫力。因此，该提案的目标是确定按摩对人体肌肉的合成代谢作用，并确定按摩释放的电动汽车是否是这种机械疗法对肌肉以及其他器官产生有益影响的候选者。神经元活动的贡献也将被研究。在目标 1 中，我们将提出以下假设：按摩通过将蛋白质生物发生转向合成代谢来充当机械疗法。使用新型按摩装置，我们将通过单侧下肢悬吊和确定的肌肉大小调节机制对正在萎缩的肌肉施加机械负荷。蛋白质合成将是主要结果。在探索性目标 2 中，我们将测试按摩通过电动汽车或神经元活动的变化引起交叉效应的假设。我们将测量血清中的 EV 及其 miRNA 货物，以及来自目标 1 的人类受试者肌肉中 EV 生物发生的标记。还将测量对侧肢体的肌肉激活。这项研究的结果不仅将表明按摩等机械疗法如何在废用期间减轻萎缩并增强合成代谢过程，而且还将确定电动汽车是否是按摩整体健康益处的候选机制。此应用程序直接解决国家补充和综合健康中心的以下计划公告中规定的目标：PA-18-322 健康：身心方法的基础科学研究 (R21)。