许多间质性肺疾病的纤维化表现以临近胸膜为主，胸膜的变化是否在肺纤维化发病中起作用是一个让研究者无法回避的问题。在对"腹腔多次注射博莱霉素、气管内一次性灌注博莱霉素"两种方法复制肺纤维化模型的研究中，我们发现无论肺组织切片视野内能否见到肺纤维化病灶，胸膜部位均可见到明显的纤维化表现，强烈提示胸膜局部对病理刺激非常敏感。他人的研究已经证实胸膜间皮细胞受损可能介导炎症反应，我们既往的研究证实胸膜间皮细胞还可以作为抗原提呈细胞介导淋巴细胞活化。我们的预实验也提示博莱霉素导致了胸膜屏障的完整性破坏、胸膜间皮细胞间连接蛋白受损、并诱导胶原的过度产生。因此，本项目拟从细胞水平、整体水平及利用临床标本展开深入研究，以验证"胸膜间皮屏障破坏、介导放大炎症反应、过度分泌细胞外基质可能是胸膜间皮细胞参与胸膜下肺纤维化发生的机制"的创新性假说，项目的开展可为肺纤维化的防治提供新的靶点。

Many interstitial pulmonary diseases presented as subpleural or pleural fibrosis, the role of pleural destruction in the pathogenesis of pulmonary fibrosis is an emerging issue for researchers. We made two types of pulmonary fibrosis animal model: multiple injection of bleomycin intraperitoneally and one time administration of bleomycin intratracheally, and found obvious pleural or subpleural fibrosis, no matter whether accompanied by pulmonary interstitial fibrosis focus, suggest strongly that pleura responsed to injury very sensitively. Others have reported that pleural mesothelial cell (PMC) injury induced inflammatory response, our previous results showed that PMCs act as antigen presenting cells in activating lymphocytes. Our preliminary experiments showed that bleomycin induced pleural barrier destruction, PMC junction protein down-regulation and Type I collagen up-regulation. Therefore, we plan to use cellular, in vivo and clinical studies to confirm the innovative hypothesis that "pleural barrier destruction amplifying inflammatory response and releasing excessive extracellular matrix maybe contribute to the mechanisms of PMC participate in the pathogenesis of pulmonary fibrosis". This project will offer a new target for the prevention and treatment of pulmonary fibrosis.