Patel Hemang, Kwon Soonjo
Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA.
Cell Mol Bioeng. 2009 Dec 1;2(4):615-624. doi: 10.1007/s12195-009-0092-4.
Ventilator-induced lung overdistension has been a growing concern in the management of mechanically ventilated patients. Mechanical ventilation triggers or enhances the net inflammatory and tissue remodeling activities. Although it has been shown that proinflammatory and tissue remodeling factors play important roles during airway remodeling, the interplay between them is not well understood. Thus, our objective was to study and characterize the molecular mechanism of cyclic equibiaxial deformation-induced airway inflammation and remodeling either in the presence or absence of a pre-existing inflammatory condition. This study was done using an dynamic model, which can simulate different mechanical ventilative conditions. Type II alveolar epithelial cell (A549) monolayers were exposed to the different levels of mechanical ventilative conditions using the Flexcell Tension Plus 4000T system, which generated the different levels of cyclic equibiaxial deformation (5, 10, 15, and 20%) at 0.2 Hz deformation frequency. The production of nitric oxide (NO), the expression of metalloprotease-2 (MMP-2)/tissue inhibitor metalloprotease-2 (TIMP-2), and the activation of MMP-2 were measured under the different levels of cyclic equibiaxial deformation either in the presence or absence of TNF-. Our study indicated that cyclic equibiaxial deformation-induced production of NO and MMP-2/TIMP-2. Higher levels of cyclic equibiaxial deformation increased the expression of the active form of MMP-2. In particular, in the presence of TNF-, the more active form of MMP-2 was detected during both cyclic equibiaxial deformation and remodeling periods.
在机械通气患者的管理中，呼吸机诱导的肺过度扩张一直是一个日益受到关注的问题。机械通气会触发或增强净炎症和组织重塑活动。尽管已经表明促炎和组织重塑因子在气道重塑过程中起重要作用，但它们之间的相互作用尚未得到充分理解。因此，我们的目标是研究并表征在存在或不存在预先存在的炎症状态下，周期性等双轴变形诱导的气道炎症和重塑的分子机制。本研究使用了一个动态模型，该模型可以模拟不同的机械通气条件。使用Flexcell Tension Plus 4000T系统将II型肺泡上皮细胞（A549）单层暴露于不同水平 的机械通气条件下，该系统在0.2Hz变形频率下产生不同水平的周期性等双轴变形（5%、10%、15%和20%）。在存在或不存在肿瘤坏死因子（TNF-）的情况下，在不同水平的周期性等双轴变形下测量一氧化氮（NO）的产生、金属蛋白酶-2（MMP-2）/金属蛋白酶组织抑制剂-2（TIMP-2）的表达以及MMP-2的激活。我们的研究表明，周期性等双轴变形诱导了NO和MMP-2/TIMP-2的产生。更高水平的周期性双轴变形增加了MMP-2活性形式的表达。特别是，在存在TNF-的情况下，在周期性等双轴变形和重塑期间均检测到更具活性形式的MMP-2。
