Utilizing the oxygen cascade to understand the biology of exercise

利用氧气级联了解运动的生物学原理

• 批准号: RGPIN-2019-04615
• 负责人: Dominelli, Paolo
• 金额: $ 2.04万
• 依托单位: University of Waterloo
• 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=682960
• 关键词: Utilizing; oxygen; cascade; understand; biology

Exercise is a powerful physiological stressor that can be utilized to address questions of basic biology. Similarly, hypoxia also provides a potent physiological stimulus and can be combined with exercise to significantly stress biological systems. The oxygen cascade' describes the physiological processes permitting environmental oxygen to be delivered and used by working muscle and is fundamental to basic biology. Determining the specific role of each aspect and/or the limiting step' in the oxygen cascade and how it influences exercise has been a long-standing question for animal and human physiologists. The LONG-TERM OBJECTIVE of my research program is to understand the mechanisms of oxygen transport and utilization under physiologically relevant conditions of exercise and hypoxia. The overarching approach of my program is to study conductance of oxygen (ventilation, pulmonary, cardiac and muscle) and their interaction. Over the next 5 years, my SHORT-TERM RESEARCH OBJECTIVE is to investigate the interaction between the oxygen cascade and exercise by using three distinct but inter-related aims. Each aim will utilize either natural (Aim 1 & 3) or pharmacologically-induced (Aim 2) variations in human anatomy and physiology and investigate the resultant effects on oxygen conductance and the integrative exercise response. Aim 1: To exploit the known sex-differences in airway anatomy and gas exchange to better understand how the pulmonary system limits oxygen transport and utilization during exercise. Aim 2 will use a pharmacological approach to manipulate blood gas homeostasis and determine how this contributes skeletal muscle force production and exercise tolerance in normoxia and hypoxia. Aim 3: Will utilize humans with naturally altered hemoglobin affinity to determine the interaction between oxyhemoglobin affinity and the oxygen cascade during exercise and acute hypoxia. The aims are linked by manipulation of the oxygen cascade, but through different mechanisms. By utilizing different manipulations my research program can probe each aspect of the oxygen cascade in isolation or combined to study integrative human physiology. Overall my research program will seek to identify the role of each step' in the oxygen cascade during exercise by using novel methods and integrative experimental approaches. Each aim is designed to ensure significant training opportunity for undergraduate and graduate HQP.********

锻炼是一种强大的生理压力源，可以用来解决基础生物学问题。同样，低氧也提供了一种强大的生理刺激，并可以与运动相结合，显著增加生物系统的压力。氧级联‘描述了允许环境中的氧气被工作肌肉输送和利用的生理过程，是基础生物学的基础。对于动物和人类生理学家来说，确定氧级联中每个方面和/或限制步骤的具体作用以及它如何影响运动一直是一个长期存在的问题。我的研究计划的长期目标是了解在生理相关的运动和低氧条件下氧的运输和利用的机制。我的计划的主要方法是研究氧气的传导性(呼吸、肺、心脏和肌肉)以及它们之间的相互作用。在接下来的5年里，我的短期研究目标是通过三个不同但相互关联的目标来研究氧级联和运动之间的相互作用。每个目标将利用人体解剖学和生理学中的自然变化(目标1和目标3)或药物诱导的变化(目标2)，并研究其对氧气传导性和综合运动反应的影响。目的1：利用已知的在呼吸道解剖和气体交换方面的性别差异，更好地了解在运动中肺系统如何限制氧气的运输和利用。目标2将使用一种药理学方法来控制血气平衡，并确定这如何在常氧和低氧条件下促进骨骼肌力产生和运动耐量。目的3：将利用具有自然变化的血红蛋白亲和力的人类来确定氧合血红蛋白亲和力与运动和急性缺氧时氧级联之间的相互作用。这些目标通过操纵氧级联联系在一起，但通过不同的机制。通过使用不同的手法，我的研究程序可以单独或结合起来探索氧级联的各个方面，以研究综合人体生理学。总体而言，我的研究计划将寻求通过使用新的方法和综合的实验方法来确定运动过程中氧级联中每一步的作用。每个目标都旨在确保本科生和研究生HQP获得重要的培训机会。