中文摘要：

背景导致 Bleomycin 的纤维变性广泛地被用来为空隙的肺的纤维变性的致病的方面建模。这研究试图在 mice.Methods 在 导致bleomycin 的肺的纤维变性上决定 simvastatin 的有益的效果和机制 导致Bleomycin 的肺的纤维变性老鼠在不同剂量与 simvastatin 被管理因为 28 days.We 测量了煽动性的反应， fibrogenic cytokines 和 profibrogenic 标记在 刺激bleomycin 并且控制肺，并且相关有肺的 fibrosis.Results Simvastatin 的这些参数稀释了组织病理学说的变化 导致bleomycin 而且， simvastatin 下面调整转变生长 factor-1 (TGF-1 ) 的增加的表示和 bleomycin 在基因和蛋白质导致的结缔组织生长因素(CTGF ) 铺平。同时， neutrophils 和淋巴细胞和肿瘤坏死因素的增加的生产的累积 --(](TNF -- 一) 在支气管的牙槽的 lavage，液体被 simvastatin 在 bleomycin 以后在早煽动性的阶段禁止注入。simvastatin 的更高的剂量在这些与更重要的减小被联系煽动性并且 fibrotic 参数。而且， p38，表明小径的 RhoA 和 Smad2/3 的 inactivation 在 simvastatin administration.Conclusions Simvastatin 期间被观察稀释了导致 bleomycin 的肺的纤维变性，在 Ashcroft 由减少显示了分数和肺骨胶原累积。肺的纤维变性的前进上的 simvastatin 的禁止的效果可以被减少 TGF-I 和 CTGF 的煽动性的反应和生产表明。这些调查结果显示 simvastatin 可以在肺的纤维变性的处理被使用。

英文摘要：

Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycininduced pulmonary fibrosis in mice. Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis. Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen （Ⅰ and Ⅲ） mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-β1 （TGF-β1） and connective tissue growth factor （CTGF） induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-a （TNF-α） in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration. Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-β1 and CTGR These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.