Analysis of Intra-cellular signaling pathway and gene network in acute lung injury as for therapeutic strategy.

ARDS后肺纤维化的发病率和病死率较高。我们认为，研究肺纤维化的发生机制和导致纤维化的关键分子将有助于ARDS的治疗。采用大鼠肺纤维化模型，皮下植入渗透泵，持续给予博莱霉素。博莱霉素致大鼠肺纤维化8天后，气管内注射角质形成细胞生长因子(KGF)重组腺病毒载体。治疗组表现为肺纤维化减轻、氧合障碍和死亡率。经KGF载体注射后，肺组织中转化生长因子-β升高，提示肿瘤坏死因子-β在肺纤维化中的重要作用。提示上皮生长因子对ARDS有肺保护作用。

Lung fibrosis following ARDS has high morbidity and mortality. We thought that investigation on the mechanism on lung fibrosis and key molecules causing fibrosis should be of benefit to ARDS treatments. Giving bleomycin continuously using an osmotic pump implanted subcutaneously, we crated pulmonary fibrosis on rats. Eight days after the administration of bleomycin when lung fibrosis occurs, rats were given keratinocyte growth factor (KGF) expressing adenovirus vector intratracheally. The treatment group expressed attenuated pulmonary fibrosis, oxygenation impairment, and mortality. Transforming growth factor (TGF)-beta that increased in lungs after the administration of bleomycin was reduced with KGF vector administration, which suggested the importance of TNF-beta on pulmonary fibrosis. These observations suggested the lung protective effects of epithelial growth factor on ARDS.