肺纤维化是最常见的肺间质疾病，也是一组由多种病因引起的慢性肺部疾病。矽肺作为肺纤维化的代表性疾病之一，是我国发病率最高、危害最为严重的职业病。研究矽尘致肺纤维化的分子机制，是探索矽肺防治措施的重要途径和手段。本课题组前期体外试验表明，酸性鞘磷脂酶（ASMase）激活在矽尘致小鼠胚肺成纤维细胞（NIH3T3）纤维化中发挥一定作用，但其代谢产物神经酰胺（Ceramide）及下游鞘磷脂类在矽肺纤维化过程中的作用及其机制尚不清楚，酸性神经酰胺酶（ACDase）抗氧化和抗纤维化作用亟待阐明。本研究拟通过运用体内与体外试验相结合的方法，采用生物化学与分子生物学技术和方法，研究ASMase/ceramide信号通路在矽尘致肺纤维化的作用及其机制，评价给予ASMase抑制剂与外源性ACDase对实验性矽肺的抗氧化损伤及抗纤维化效应。本研究为阐明矽肺的分子机制提供科学依据，为矽肺纤维化的防治提供新的线索。

Pulmonary fibrosis, the most common interstitial lung disease, is also a group of chronic lung diseases caused by a variety of causes. As one of the representative disease of pulmonary fibrosis, Silicosis is the most serious and terrible occupation disease with the highest incidence in our country. Exploring the molecular mechanisms of silica dust -induced pulmonary fibrosis have became the important means to study the prevention and cure measures for silicosis. The preliminary data in vitro of our research group showed that the activation of acid sphingomyelinase(ASMase) played a role in silica-induced fibrosis in mouse embryonic fibroblast ( NIH3T3), but the effect and the related mechanism of its important metabolites amide (Ceramide) and the downstream sphinglipids on silicosis fibrosis remain to be explored, the role of Acid ceramidase(ACDase) in the anti- oxidation and anti-pulmonary fibrosis and the related mechanism deserve in-depth study and further exploration. By using the biochemistry and molecular biology techniques and methods in vitro and in vivo, the present study aims to explore the role and related mechanism of ASMase/ceramide pathway in silicon dioxide dust-induced pulmonary fibrosis, and to evaluate the effect of ASMase inhibitor and exogenous ACDase on the anti-oxidation and anti-pulmonary fibrosis in experimental silicosis. The present research will provide experimental evidence for the further exploration of the molecular mechanisms of pulmonary fibrosis, and will also shed lights on the new important clue for the prevention and cure measures for silicosis.