Berg J T, Fu Z, Breen E C, Tran H C, Mathieu-Costello O, West J B
Department of Medicine, University of California San Diego, La Jolla, California 92093-0623, USA.
J Appl Physiol (1985). 1997 Jul;83(1):120-8. doi: 10.1152/jappl.1997.83.1.120.
Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alpha2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.
慢性毛细血管压力升高（如二尖瓣狭窄）后会发生肺毛细血管重塑。此外，肺动脉重塑在壁应力增加后4小时内开始，且依赖于内皮细胞。我们之前已经表明，高肺膨胀会增加肺毛细血管的壁应力。本研究旨在确定高肺膨胀是否会诱导肺实质细胞外基质（ECM）重塑。对开胸兔进行通气，一侧肺采用9 cmH2O呼气末正压（PEEP），另一侧肺采用1 cmH2O PEEP通气4小时（高PEEP组），或两侧肺均采用2 cmH2O PEEP通气（低PEEP组）。另外还设立了一个未处理的对照组。我们发现，高PEEP兔双肺中α1(III)和α2(IV)前胶原、纤连蛋白、碱性成纤维细胞生长因子和转化生长因子-β1的mRNA水平均升高（与低PEEP组和未处理组相比）。相比之下，α2(I)前胶原和血管内皮生长因子的mRNA水平没有变化。我们得出结论，4小时的高肺膨胀会增加肺实质中ECM成分和生长因子的mRNA水平。
