Airway compliance measurements in mouse models of respiratory diseases.
Airway compliance measurements in mouse models of respiratory diseases.
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呼吸道疾病小鼠模型的气道顺应性测量。
DOI：
10.1152/ajplung.00470.2020
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Mitzner,Wayne
中科院分区：
文献类型：
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作者：
Robichaud,Annette;Fereydoonzad,Liah;Collins,SamuelL;Loube,JeffreyMartin;Ishii,Yumiko;Horton,MaureenR;Martin,JamesG;Mitzner,Wayne
气道顺应性（Caw）的定量是研究疾病模型气道变化的基础。然而，在小鼠中难以获得所需的气道压力和容积测量值。我们假设，全范围压力-容积（PV）曲线的充气分支可用于量化Caw，因为它包含一个只有气道树扩张的片段。研究目的是通过分析先前在三种小鼠模型中收集的全范围PV曲线来评估该方法的可行性：肺气肿的弹性蛋白酶模型、自发发生肺气肿的遗传模型（白三烯C4合酶敲除; LTC 4S-KO）和肺纤维化的博来霉素模型。实验结果验证了Caw相对于呼吸系统顺应性（ΔCaw/ΔC）、呼吸分钟功（mWOB）和20.5 Hz时的弹性（Ers_20.5）的变化，Caw估计为健康小鼠总顺应性的3%或2.3 ± 1 μL/cmH 2 O（n= 17）。该技术检测了相对于对照小鼠的呼吸道阻塞性和限制性疾病模型的变化以及所研究的两种肺气肿模型的差异。Caw的变化与ΔCaw/ΔC、mWOB或Ers_20.5中观察到的变化一致，根据模型以及人类和小鼠文献中报告的结果存在一些变化。DirectCaw测量小至小鼠的受试者可能被证明有助于进一步表征与气道重塑相关的其他呼吸系统疾病模型或评估治疗效果。
The quantification of airway compliance (Caw) is essential to the study of airway alterations in disease models. However, the required measurements of airway pressure and volume are difficult to acquire in mice. We hypothesized that the inflation limb of full-range pressure-volume (PV) curves could be used to quantifyCaw, as it contains a segment where only the airway tree is distended. The study objective was to assess the feasibility of the approach by analysis of full-range PV curves previously collected in three mouse models: an elastase model of emphysema, a genetic model spontaneously developing emphysema (leukotriene C4 synthase knockout; LTC4S-KO), and a bleomycin model of lung fibrosis. Attempts to validate results includedCawchange relative to respiratory system compliance (ΔCaw/ΔC), the minute work of breathing (mWOB), and the elastance at 20.5 Hz (Ers_20.5) from prior respiratory mechanics measurements in the same subjects.Cawwas estimated at 3% of total compliance in healthy mice or 2.3 ± 1 μL/cmH2O (n= 17). The technique detected changes in models of respiratory obstructive and restrictive diseases relative to control mice as well as differences in the two emphysema models studied. The changes inCawwere consistent with those seen in ΔCaw/ΔC, mWOB, orErs_20.5, with some variations according to the model, as well as with results reported in the literature in humans and mice. DirectCawmeasurements in subjects as small as mice could prove useful to further characterize other respiratory disease models associated with airway remodeling or to assess treatment effects.