The physiological role of airway smooth muscle

呼吸道平滑肌(ASM)在气道树上可见。尽管它的结构很复杂，定义也很明确，但它难以捉摸的功能几十年来一直困扰着世界上最好的生理学家。目前的建议是一个正在进行的由NSERC资助的项目的更新，其长期目标是阐明ASM的生理作用。我们最近使用一种体外环境来研究ASM的动态行为，这种环境可以模拟呼吸过程中肺的不断运动。结果提示，ASM在呼吸动作中起到稳定呼吸道管径的作用。如何调整这种稳定功能以适应更大的通风，例如在体育锻炼期间，仍有待研究。 除了继续我们的体外研究外，我们还建议扩大我们的范围，包括在小鼠体内进行的实验。总体而言，我们提出了两个短期目标。第一个目标是更详细地研究ASM在我们的体外环境中可以模拟肺运动的稳定功能。第二个目标是评估在体外的发现如何影响体内小鼠整个呼吸系统的力学。该计划的功能方案可以被视为一个连续体，其中最有希望的体外发现随后在体内进行研究。因此，虽然在体外不断探索新的途径，但体内的工作是由我们最重要的体外发现推动的。 使用了各种方法。由于ASM的收缩能力不能在体内直接测量，我们依赖尖端技术。这些技术是多年工程、计算建模和实验生物学的产物。它们现在提供了间接测量，从中我们可以推断ASM在活体中所起的综合作用。我们提出的一些实验实际上旨在充分利用这些技术的能力，以进一步了解ASM影响呼吸系统的复杂方式。我们的数据集还将被用来进一步完善目前在呼吸力学领域使用的计算模型，以推断ASM的作用。 该计划在知识进步、科学出版物以及产生新的想法和假设方面是富有成效的。这也有利于重要的发现，这些发现有可能显著改变呼吸力学领域。最后，该计划成功地培养了位于生物学和工程学交界处的高素质人才(HQP)。更具体地说，HQP获得了在孤立的情况下仔细检查机械活动组织的行为的技能，然后研究这些行为如何与其他呼吸系统组织相互作用，最终影响整个呼吸系统的功能。

Airway smooth muscle (ASM) is found all along the airway tree. Although its structure is elaborated and well defined, its elusive function has been perplexing the world's best physiologists for many decades. The present proposal is a renewal of an ongoing NSERC-funded program with the long-term objective to elucidate the physiological role of ASM. We have recently studied the dynamic behaviors of ASM using an in vitro setting that can mimic the ceaseless movements of the lungs during breathing. The results suggested that ASM serves to stabilize the caliber of the airways during breathing maneuvers. How this stabilizing function can be adjusted to accommodate greater ventilation, such as during a physical exercise, remains to be studied. In addition to pursue our in vitro investigations, we propose to broaden our scope by including experiments conducted in vivo in mice. Overall, we propose 2 short-term objectives. The 1st objective is to study in greater detail the stabilizing function of ASM in our in vitro setting that can mimic lung movements. The 2nd objective is to evaluate how the findings made in vitro affect the mechanics of the whole respiratory system in mice in vivo. The functional scheme of the program can be seen as a continuum, where the most promising findings made in vitro are subsequently investigated in vivo. Therefore, while new avenues are continuously explored in vitro, the work in vivo is motivated by our most important in vitro findings. A variety of methodologies are used. Since the contractility of ASM cannot be measured directly in vivo, we rely on cutting-edge technologies. These technologies are the products of many years of engineering, computational modeling and experimental biology. They now provide indirect measurements from which we can deduce the integrated role played by ASM in vivo. Some of the experiments we propose actually aim at exploiting the full capacity of these technologies to gain further insights on the intricate ways by which ASM influences the respiratory system. Our data set will also be exploited to further refine the computational models that are currently used in the field of respiratory mechanics to infer the role of ASM. The program is productive in terms of knowledge advancements, scientific publications and generation of new ideas and hypotheses. It is also conducive to important discoveries that have the potential to significantly change the field of respiratory mechanics. Finally, the program successfully trains highly qualified personnel (HQP) in a field that lies exactly at the interface between biology and engineering. More specifically, the HQP acquires the skills to scrutinize the behaviors of a mechanically active tissue in isolation, and to then study how these behaviors interact with other respiratory tissues to ultimately influence the function of the whole respiratory system.