Protective mechanisms of skeletal muscle against oxidative stress by physical exercise: the role of uncoupling protein via NO

运动被认为是预防和治疗与生活方式有关的疾病的有用工具之一。另一方面，体育锻炼显著增强骨骼肌中的血液流动，从而导致活性氧物种(ROS)的产生增加。2003年，我们证明了急性离心性运动增加小鼠骨骼肌ROS的产生可能是由于白细胞以外的其他因素，细胞外超氧化物歧化酶(EC-SOD)参与了运动的抗动脉硬化作用。出乎意料的是，运动后小鼠骨骼肌解偶联蛋白(UCP2和UCP3)或一氧化氮合酶(NOS-I、II、III)没有显著变化。实施的体能训练包括30min的间歇训练(游泳或跑步)和30min的长距离训练(游泳或跑步)，每周5次，每天30min，共3个月。在训练前后进行肌肉活组织检查。所有受试者的VO_2max水平均显著升高，表明有氧能力有所改善。训练后，热休克蛋白70、铜锌超氧化物歧化酶和锰超氧化物歧化酶的mRNAs表达显著降低，而UCP2mRNAs的表达显著增加，而血管内皮生长因子、碱性成纤维细胞生长因子、HIF1α、肌红蛋白和UCP3mRNAs的水平没有明显变化。此外，训练后HIF1VEGFmRNA表达的变化与α表达的变化有很好的相关性。在训练过程中，UCP2基因表达的增加可能减弱了ROS的产生。综上所述，可以预见，在从连续的运动中恢复期间，转录的瞬时变化的累积效应可能代表与耐力训练相关的细胞适应的潜在动力学基础。

Exercise is considered to serve as one of useful tools for the prevention and remedy against lifestyle-related diseases. On the other hand, physical exercise markedly enhances a flow of blood in skeletal muscle, thereby leading to an increase in the production of reactive oxygen species (ROS). In 2003 we demonstrated that the increased production of ROS by acute eccentric exercise in mouse skeletal muscle might be due to factors other than leukocytes, and that extracellular superoxide dismutase (EC-SOD) had a part in antiarteriosclerotic effects of exercise. Unexpectedly, there were no significant changes in uncoupling proteins (UCP2 and UCP3) or nitric oxide synthases (NOS-I, II, III) in skeletal muscle from mice after the exercise.In 2004 we made a human study. The physical training executed consisted of 30-min interval training (swimming or running) in addition to 30-min long-distance training (swimming or running) per day, 5 times per week, during 3 months. Muscle biopsies were taken before and after the training. All the subjects notably increased their VO_2max levels, indicating an improvement in aerobic capacity. After training, there were significant decreases in the expression of mRNAs for HSP70, CuZn-SOD, and Mn-SOD but a significant increase in UCP2 mRNA expression, whereas no definite changes were observed in the levels of mRNAs for VEGF, bFGF, HIF1α, myoglobin, or UCP3. Moreover, the changes in HIF1α mRNA expression correlated well with those in VEGF mRNA expression after training. The increased expression of UCP2 mRNA might attenuate the generation of ROS during the training period. Taken together, it is envisioned that cumulative effects of transient changes in transcription during recovery from successive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with endurance training.