ANABOLIC RESPONSE TO EXERCISE TRAINING IN HEMODIALYSIS

血液透析中运动训练的合成代谢反应

• 批准号: 7376041
• 负责人: JOEL DAVID KOPPLE
• 金额: $ 0.5万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376041
• 关键词: ANABOLIC; RESPONSE; EXERCISE; TRAINING; HEMODIALYSIS

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. Maintenance hemodialysis (MHD) patients often complain of malaise, weakness and exercise intolerance and display a myopathy. Endurance exercise training (ET) and erythropoietin improve their endurance capacity, but not to normal. Our pilot study in MHD patients indicates that endurance exercise training (ET) decreases gene expression for myostatin, a protein that suppresses skeletal muscle hypertrophy, and increases mRNA for insulin-like growth factor-I (IGF-I) and the IGF-receptor (IGF-R). This project will examine the primary hypothesis that in MHD patients strength training (ST), ET or a combination of ST and ET, as compared to no training (NT), leads, in skeletal muscle, to decreased mRNA for myostatin. The main secondary hypothesis are that, in skeletal muscle, ST, ET and a combination of ET and St, as compared to NT, increase mRNA for IGF-I, IGF-R, and myosin heavy chains and the IGF-I, IGF-R, and myosin heavy chain proteins and decrease myostatin. It is further hypothesized that ET, ST and a combination of ET and ST will alter nRNA for IGF binding proteins, cause skeletal muscle hypertrophy (as determined by cross-sectional muscle fiber area, DEXA, anthropometry), and improve skeletal muscle morphology (as indicated by a more normal proportion of type IIa/IIx fibers and mitochondrial structure) and biochemistry (e.g., increased succinate dehydrogenase activity); also that endurance and strength capacity and other clinical variables will improve. It is hypothesized that ST will have a greater effect on muscle strength and processes associated with skeletal muscle hypertrophy, whereas ET will promote greater endurance exercise capacity and muscle aerobic enzyme activity (e.g., succinate dehydrogenase activity). The combination of ET and ST, by combining the elements of both exercise training regimens, will improve both types of processes. Also, a combination of ET and ST and, to a lesser degree, ST and ET employed separately, will make most of these measures more similar to those of healthy, non-exercise trained adults. Clinically stable MHD patients will enter a baseline phase where initial measurements are obtained and relevant clinical variables are standardized. Patients will then be randomized to receive ST, ET, ET and ST or NT (20 patients per group) for 6 months. ST, ET or the combination of ET and ST will be performed thrice-weekly for up to 40 minutes, before or during the first 90 minutes of MHD. Outcome measures will then be repeated; measures from the four treatment groups will be compared to each other and to healthy adults.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。维持性血液透析（MHD）患者常主诉不适、虚弱和运动不耐受，并表现为肌病。耐力运动训练（ET）和促红细胞生成素能提高他们的耐力，但不能达到正常水平。我们在MHD患者中的初步研究表明，耐力运动训练（ET）降低肌肉生长抑制素（一种抑制骨骼肌肥大的蛋白质）的基因表达，并增加胰岛素样生长因子- i （IGF-I）和igf受体（IGF-R）的mRNA表达。本项目将检验MHD患者力量训练（ST）， ET或ST和ET的组合，与没有训练（NT）相比，导致骨骼肌中肌生成抑制素mRNA降低的主要假设。主要的次要假设是，在骨骼肌中，与NT相比，ST、ET以及ET和ST的组合增加了IGF-I、IGF-R和肌球蛋白重链以及IGF-I、IGF-R和肌球蛋白重链蛋白的mRNA，并降低了肌生长抑制素。进一步假设ET、ST以及ET和ST的组合会改变IGF结合蛋白的nRNA，导致骨骼肌肥大（由横断面肌纤维面积、DEXA、人体测量确定），并改善骨骼肌形态（由IIa/IIx型纤维和线粒体结构的更正常比例表明）和生物化学（例如，琥珀酸脱氢酶活性增加）；同时耐力和力量能力等临床指标也会有所提高。假设ST将对肌肉力量和与骨骼肌肥大相关的过程产生更大的影响，而ET将促进更大的耐力运动能力和肌肉有氧酶活性（例如琥珀酸脱氢酶活性）。ET和ST的结合，通过结合两种运动训练方案的元素，将改善这两种类型的过程。此外，将ET和ST结合使用，以及在较小程度上单独使用ST和ET，将使大多数这些测量更类似于那些健康的，未经运动训练的成年人。临床稳定的MHD患者将进入基线阶段，在此阶段获得初始测量值并标准化相关临床变量。患者将随机接受ST、ET、ET和ST或NT治疗（每组20例），为期6个月。ST， ET或ET和ST的组合将在MHD前90分钟或期间每周进行三次，每次不超过40分钟。然后将重复结果测量；四个治疗组的测量结果将相互比较，并与健康成年人进行比较。