Cardiovascular and muscle oxidative adaptations to exercise

心血管和肌肉对运动的氧化适应

• 批准号: RGPIN-2017-06560
• 负责人: Boushel, Robert
• 金额: $ 2.84万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687297
• 关键词: Cardiovascular; muscle; oxidative; adaptations; exercise

Oxygen consumption by muscle during exercise depends on convective oxygen delivery, diffusion of oxygen from the capillaries to mitochondria and the activation state, oxygen affinity and respiratory capacity of muscle mitochondria. The long-term objective is to understand the relative contributions of the circulatory and muscle oxidative systems in defining muscle oxygen uptake in humans during acute exercise and how these systems are regulated and adapt to physical training. My short-term objectives build upon recent advances integrating components of the oxygen cascade that center on two main themes.****Theme I focuses on the role the central circulation, and the mechanisms regulating regional distribution of blood flow to muscle through the interaction of autonomic nervous system and local muscle vasodilatory mechanisms. This research builds on recent work employing novel methods to quantify blood pumped by the heart, regional limb and muscle microcirculatory blood flow during exercise in humans combined with arterial and venous sampling across an exercising limb.****Theme II examines the components of oxygen diffusion from the capillaries to muscle mitochondria, and how muscle mitochondria are regulated structurally and functionally. This work integrates methods to measure blood flow in the limbs, blood sampling to measure oxygen content, and mitochondrial respiratory function in muscle biopsies.****Aim 1. The role of the circulation for increasing peak muscle oxygen uptake with training. Exercise training increases muscle mitochondrial volume and muscle oxidative capacity. However, a higher muscle oxygen uptake can be achieved through a greater distribution of blood flow to contracting muscle, a greater density of blood vessels, slowing of the rate of passage of blood cells through the muscle allow greater diffusion of oxygen and a higher relative activation of mitochondria. This research program will quantify the relative roles of the central, regional and microcirculations and muscle oxidative capacity to advance our understanding of adaptive response of the components of the oxygen cascade in humans.****Aim 2. The role of mitochondria in muscle oxygen extraction during exercise.****It has long been known that training increases muscle oxygen extraction. This research plan will examine how changes in the affinity of mitochondria for oxygen increases muscle oxygen uptake. This program of research will examine how oxygen affinity is regulated acutely by altering the rate at which mitochondria are activated. Also to be examined is whether the form of enzyme expressed in mitochondria that binds oxygen (cytochrome c oxidase) is altered over time with exercise training. Using advanced imaging with electron microscopy, changes in the volume of the inner mitochondrial membrane where most cellular energy is produced will be determined to examine a novel mechanism regulating oxygen uptake.**

运动过程中肌肉的氧消耗取决于对流氧输送、氧从毛细血管向线粒体的扩散以及肌肉线粒体的活化状态、氧亲和力和呼吸能力。 长期目标是了解循环和肌肉氧化系统在急性运动期间定义人体肌肉氧摄取的相对贡献，以及这些系统如何调节和适应体育训练。我的短期目标建立在最近的进展上，整合了围绕两个主要主题的氧气级联组件。第一主题着重于中枢循环的作用，以及通过自主神经系统和局部肌肉血管舒张机制的相互作用来调节血流向肌肉的区域分布的机制。这项研究建立在最近的工作基础上，采用新的方法来量化人体运动期间心脏，局部肢体和肌肉微循环血流泵送的血液，并结合运动肢体的动脉和静脉采样。主题二考察了氧气从毛细血管扩散到肌肉线粒体的成分，以及肌肉线粒体在结构和功能上是如何调节的。这项工作整合了测量四肢血流量的方法，血液采样以测量氧含量，以及肌肉活检中的线粒体呼吸功能。目标1.循环在训练中增加肌肉摄氧量峰值的作用。运动训练增加肌肉线粒体体积和肌肉氧化能力。然而，通过更大的血流分布到收缩的肌肉、更大的血管密度、减慢血细胞通过肌肉的速度可以实现更高的肌肉摄氧量，从而允许更大的氧气扩散和更高的相对活性线粒体。这项研究计划将量化中央，区域和微循环以及肌肉氧化能力的相对作用，以促进我们对人类氧级联组分适应性反应的理解。目标2.线粒体在运动过程中肌肉氧提取中的作用 *长期以来，人们都知道训练可以增加肌肉的氧气提取。这项研究计划将研究线粒体对氧的亲和力的变化如何增加肌肉的摄氧量。这项研究计划将研究如何通过改变线粒体被激活的速率来急性调节氧亲和力。还需要检查的是，线粒体中表达的结合氧的酶（细胞色素c氧化酶）的形式是否随着运动训练的时间而改变。使用先进的电子显微镜成像，将确定产生大部分细胞能量的线粒体内膜体积的变化，以检查调节氧摄取的新机制。