Welsh D A, Summer W R, Dobard E P, Nelson S, Mason C M
Department of Medicine, Louisiana State University Medical Center, New Orleans, Louisiana, USA.
Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1081-6. doi: 10.1164/ajrccm.162.3.9908099.
Mechanical ventilation has been shown to produce lung injury characterized by noncardiogenic pulmonary edema. Keratinocyte growth factor (KGF) is a heparin-binding growth factor that causes alveolar type II pneumocyte hyperplasia. KGF pretreatment and the resultant pneumocyte hyperplasia reduce fluid flux in models of lung injury. We utilized the isolated perfused rat lung model to produce lung injury by varying tidal volume and the level of positive end-expiratory pressure during mechanical ventilation. Pretreatment with KGF attenuated ventilator-induced lung injury (VILI). This was demonstrated by lower wet-to-dry lung weight ratios and less lung water accumulation in the KGF group. Further, KGF prevented the decline in dynamic compliance and alveolar protein accumulation in VILI. KGF pretreatment reduced alveolar accumulation of intravascularly administered fluorescein isothiocyanate-labeled high-molecular-weight dextran. Thus, pretreatment with KFG attenuates injury in this ex vivo model of VILI via mechanisms that prevent increases in permeability.
机械通气已被证明会导致以非心源性肺水肿为特征的肺损伤。角质形成细胞生长因子（KGF）是一种肝素结合生长因子，可引起II型肺泡上皮细胞增生。KGF预处理及由此产生的肺上皮细胞增生可减少肺损伤模型中的液体通量。我们利用离体灌注大鼠肺模型，通过在机械通气期间改变潮气量和呼气末正压水平来造成肺损伤。KGF预处理减轻了呼吸机诱导的肺损伤（VILI）。KGF组较低的肺湿重与干重比及较少的肺水积聚证明了这一点。此外，KGF可防止VILI中动态顺应性的下降和肺泡蛋白积聚。KGF预处理减少了血管内注射异硫氰酸荧光素标记的高分子量右旋糖酐在肺泡中的积聚。因此，KFG预处理通过防止通透性增加的机制减轻了该VILI离体模型中的损伤。
