Epithelial Cell Apoptosis Causes Acute Lung Injury Masquerading as Emphysema
Epithelial Cell Apoptosis Causes Acute Lung Injury Masquerading as Emphysema
复制标题
DOI：
10.1165/rcmb.2008-0137oc
复制
发表时间：
2009-10-01
影响因子：
6.4
通讯作者：
Shapiro, Steven D.
中科院分区：
文献类型：
--
作者：
Mouded, Majd;Egea, Eduardo E.;Shapiro, Steven D.
肺气肿的理论传统上围绕着细胞外基质的蛋白水解破坏。最近已经开发出模型，其显示了伴随肺细胞凋亡的诱导的气腔扩大。本研究的目的是确定上皮细胞凋亡模型引起空域扩大的机制。用微囊藻毒素（MC）诱导细胞凋亡、猪胰弹性蛋白酶（PPE）或其各自的载体处理小鼠。使来自所有组的小鼠膨胀，并在各个时间点测量形态测定法。对气道阻力、组织弹性和肺容量进行生理学测量。通过空气-盐水准静态测量、表面活性剂染色和表面活性剂功能研究进一步分析各组。用MC处理的小鼠显示出可逆的空域扩大的证据。相比之下，PPE治疗的小鼠表现出不可逆的空域扩大。在MC-处理的小鼠的空域扩大与非弹性回缩的增加，由于肺泡表面张力的增加。PPE处理的小鼠表现出肺弹性回缩和正常肺泡表面张力的损失，这与人类肺气肿的模式更一致。肺上皮细胞凋亡的MC模型中发生的气腔扩大显示出与人类肺气肿不同的生理学。由于表面张力变化引起的可逆性、限制性生理学和与不均匀肺泡萎陷相关的肺泡扩大与轻度急性肺损伤最为一致。接近总肺容量的充气表现为肺泡增大，因为相邻的塌陷肺泡施加束缚力。
Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air-saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase inelastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces.