A Microfluidic System to Measure Neonatal Lung Compliance Over Late Stage Development as a Functional Measure of Lung Tissue Mechanics.
A Microfluidic System to Measure Neonatal Lung Compliance Over Late Stage Development as a Functional Measure of Lung Tissue Mechanics.
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一种微流体系统，用于测量晚期发育阶段新生儿肺顺应性，作为肺组织力学的功能测量。
DOI：
10.1115/1.4047133
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Gleghorn,JasonP
中科院分区：
文献类型：
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作者：
Schappell,LaurelE;Minahan,DanielJ;Gleghorn,JasonP
早产会中断肺部的发育，导致功能缺陷和复杂病理的发生，例如支气管肺发育不良（BPD），进一步降低未成熟肺部的功能。分子靶标的失调与 BPD 的表现有关，但目前还没有方法将组织组织学中观察到的形态变化与这些扰动与整个囊泡和肺泡肺发育过程中的功能差异相关联。肺顺应性是肺机械特性的综合测量，对许多分子、细胞和结构特征高度敏感，但由于测量挑战，人们对新生小鼠肺的顺应性知之甚少。我们开发了一种新方法来量化肺容量和压力的变化，以确定整个新生小鼠肺部发育过程中的吸气和呼气顺应性。所获得的顺应性测量结果根据已发表的研究中使用细胞外基质 (ECM) 酶促降解后的成熟肺的顺应性值进行了验证。然后该系统用于量化新生小鼠肺部发育整个过程中发生的顺应性变化。这些方法填补了一个至关重要的空白，将强大的发育和疾病小鼠模型与对呼吸至关重要的功能性肺力学测量联系起来，并能够深入了解 BPD 病理学的遗传、分子和细胞基础，以改善早产儿的肺功能。
Premature birth interrupts the development of the lung, resulting in functional deficiencies and the onset of complex pathologies, like bronchopulmonary dysplasia (BPD), that further decrease the functional capabilities of the immature lung. The dysregulation of molecular targets has been implicated in the presentation of BPD, but there is currently no method to correlate resultant morphological changes observed in tissue histology with these perturbations to differences in function throughout saccular and alveolar lung development. Lung compliance is an aggregate measure of the lung's mechanical properties that is highly sensitive to a number of molecular, cellular, and architectural characteristics, but little is known about compliance in the neonatal mouse lung due to measurement challenges. We have developed a novel method to quantify changes in lung volume and pressure to determine inspiratory and expiratory compliance throughout neonatal mouse lung development. The compliance measurements obtained were validated against compliance values from published studies using mature lungs following enzymatic degradation of the extracellular matrix (ECM). The system was then used to quantify changes in compliance that occurred over the entire span of neonatal mouse lung development. These methods fill a critically important gap connecting powerful mouse models of development and disease to measures of functional lung mechanics critical to respiration and enable insights into the genetic, molecular, and cellular underpinnings of BPD pathology to improve lung function in premature infants.