Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema.
Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema.
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急性机械力导致弹性蛋白酶诱导的肺气肿中肺结构和功能恶化。
DOI：
10.1152/ajplung.00217.2012
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Suki,B
中科院分区：
文献类型：
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作者：
Szabari,MV;Parameswaran,H;Sato,S;Hantos,Z;Bartolák-Suki,E;Suki,B
慢性阻塞性肺疾病（COPD）的进展与病情加重之间的关系尚不清楚。目前，尚无慢性阻塞性肺病急性加重（AECOPD）的动物模型。本研究的目的是评估深吸气 (DI) 引起的机械力对模拟 AECOPD 的肺结构和功能短期恶化的影响。在用弹性蛋白酶处理后第2、7或21天，使用或不使用DIs对小鼠进行通气（35 cmH2O气道压力，持续3秒，2次/分钟）1小时。通过身体体积描记法测量功能残气量（FRC），并通过受迫振荡获得呼吸顺应性、阻力和迟滞性。从苏木精和伊红染色的切片中，确定了气道周围的等效空腔直径 (D)、肺泡壁厚度 (Wt)、间隔破裂数 (Nsr) 和附着密度 (Ad)。 FRC、顺应性和迟滞性在统计上随时间显着增加，并且均因 DI 而增加。有趣的是，DI 对对照小鼠的 FRC、顺应性、抵抗力和迟滞性也有影响。肺气肿的发展在统计上显着增加了D和Wtin时间，并且DI引起了D的细微差异。在21天时，DI的应用改变了D的分布，增加了Wt和Nsr，并减少了Ad。这些结果表明，一旦达到实质的关键重塑，急性机械力会导致结构和功能发生不可逆的变化，类似于慢性阻塞性肺病的恶化。因此，在肺气肿小鼠中急性应用 DI 可能作为 AECOPD 的有用模型。
The relation between the progression of chronic obstructive pulmonary disease (COPD) and exacerbations is unclear. Currently, no animal model of acute exacerbation of COPD (AECOPD) exists. The objectives of this study were to evaluate the effects of mechanical forces induced by deep inspirations (DIs) on short-term deterioration of lung structure and function to mimic AECOPD. At 2, 7, or 21 days after treatment with elastase, mice were ventilated with or without DIs (35 cmH2O airway pressure for 3 s, 2 times/min) for 1 h. Functional residual capacity (FRC) was measured with body plethysmography, and respiratory compliance, resistance, and hysteresivity were obtained via forced oscillations. From hematoxylin and eosin-stained sections, equivalent airspace diameters (D), alveolar wall thickness (Wt), number of septal ruptures (Nsr), and attachment density (Ad) around airways were determined. FRC, compliance, and hysteresivity statistically significantly increased with time, and both increased due to DIs. Interestingly, DIs also had an effect on FRC, compliance, resistance, and hysteresivity in control mice. The development of emphysema statistically significantly increased D and Wtin time, and the DIs caused subtle differences in D. At 21 days, the application of DIs changed the distribution of D, increased Wtand Nsr, and decreased Ad. These results suggest that once a critical remodeling of the parenchyma has been reached, acute mechanical forces lead to irreversible changes in structure and function, mimicking COPD exacerbations. Thus, the acute application of DIs in mice with emphysema may serve as a useful model of AECOPD.