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，其中肝流入短暂中断两次，持续15分钟。在肝缺血再灌注和假手术（分别为NC-LT和NC-HT）后，分别评估6 ml/kg （IR-LT）和24 ml/kg （IR-HT）两种潮气量。在4组中，只有IR-HT组发生肺损伤，通过肺干湿比增加、存在明显的组织病理学变化（如血管周围水肿和血管内白细胞聚集）以及BAL液TNF-α浓度增加来评估。这些结果提示肝脏缺血再灌注引起全身性炎症，肝缺血再灌注后高潮气量通气可触发肺损伤。腺病毒介导的角化细胞生长因子（keratinocyte growth factor， KGF） cDNA转染成功地在气道上皮细胞中表达了高水平的KGF，从而显著提高了肺上皮细胞的增殖，改善了氧合，降低了死亡率。此外，载体相关炎症最小。我们认为，将KGF基因转导到肺中是治疗急性肺损伤的一种有希望的潜在方法，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.