ANABOLIC RESPONSE TO EXERCISE TRAINING IN HEMODIALYSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。维持性血液透析（MHD）患者经常主诉不适、虚弱和运动不耐受，并显示肌病。耐力运动训练（ET）和促红细胞生成素能提高运动员的耐力，但不能使其恢复正常.我们对MHD患者的初步研究表明，耐力运动训练（ET）降低了肌肉生长抑制素（一种抑制骨骼肌肥大的蛋白质）的基因表达，并增加了胰岛素样生长因子-I（IGF-I）和IGF-R的mRNA。该项目将检验MHD患者中的主要假设，即与无训练（NT）相比，力量训练（ST）、ET或ST和ET的组合导致骨骼肌中肌生长抑制素的mRNA降低。主要的次要假设是，在骨骼肌中，与NT相比，ST、ET和ET与St的组合增加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，并减少肌生长抑制素。进一步假设ET、ST以及ET和ST的组合将改变IGF结合蛋白的nRNA，引起骨骼肌肥大（如通过横截面肌纤维面积、DEXA、人体测量所确定的），并改善骨骼肌形态（如通过IIa/IIx型纤维和线粒体结构的更正常比例所指示的）和生物化学（例如，琥珀酸脱氢酶活性增加）;耐力和力量能力以及其他临床变量也将改善。假设ST将对肌肉力量和与骨骼肌肥大相关的过程具有更大的影响，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，将改善两种类型的过程。此外，ET和ST的组合，以及在较小程度上，ST和ET单独使用，将使大多数这些措施更类似于健康的，非运动训练的成年人。临床稳定的MHD患者将进入基线期，获得初始测量值，并对相关临床变量进行标准化。然后将患者随机接受ST、ET、ET和ST或NT（每组20例患者）治疗6个月。ST、ET或ET和ST的组合将在MHD的前90分钟之前或期间每周进行三次，最长40分钟。然后将重复结果测量;将四个治疗组的测量结果相互比较并与健康成人进行比较。

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.