Basic research on novel therapeutic approaches to lung injury associated with Legionella pneumophilia pneumonia.

我们研究了麻醉和机械通气的大鼠，在这些大鼠中，肝脏流入被短暂中断两次，持续15分钟。测定肝脏缺血再灌流后和假手术后的潮气量，分别为6ml/kg(IR-LT)和24ml/kg(IR-HT)。在4组中，只有IR-HT组发生了肺损伤，表现为肺湿/干重比增加，出现明显的组织病理学改变，如血管周围水肿和血管内白细胞聚集，以及肺泡灌洗液中肿瘤坏死因子-α浓度的增加。这些结果表明，肝脏缺血再灌注引起全身炎症反应，大潮气量换气引起肺损伤。腺病毒介导的角质形成细胞生长因子(KGF)基因在呼吸道上皮细胞中高水平表达角质形成细胞生长因子(KGF)，从而显著促进肺上皮细胞增殖，改善氧合，降低死亡率。此外，与病媒相关的炎症也很少。我们认为，肺内转导KGF基因是治疗急性肺损伤的一种有前景的治疗方法，并将成为再生研究的有用工具。

We studied anesthetized and mechanically ventilated rats, in which the hepatic inflow was transiently interrupted twice for 15 minutes. Two tidal volumes, 6 ml/kg (IR-LT) and 24 ml/kg (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation (NC-LT and NC-HT, respectively). Of the 4 groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet to dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the BAL fluid TNF-α concentration. These findings suggest that liver ischemia-reperfusion caused systemic inflammation, and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.Adenovirus-mediated transfer of keratinocyte growth factor (KGF) cDNA successfully expressed high level of KGF in airway epithelial cells, and consequently raised significant lung epithelial cell proliferation, improved oxygenation, and decreased mortality. Furthermore, there was minimal vector-associated inflammation. We suggest that KGF gene transduction into lungs is a promising potential treatment for acute lung injury and would be a useful tool for regeneration research.