矽肺是由于在生产过程中吸入大量矽尘而导致的以肺部慢性炎症和肺组织纤维化为主要病理改变的尘肺病。矽肺患者约占我国尘肺总病例的50%，是危害最严重的一种职业病。但目前矽肺的发病及免疫调控机制尚不明确。我们前期研究发现，矽肺患者肺泡巨噬细胞自噬活动的异常可能在矽肺发生发展中具有关键作用，而薯蓣皂苷可能通过调控自噬在矽肺发生发展中发挥保护作用，但其具体分子机制尚不清楚。本项目在前期工作基础上，拟综合运用免疫、分子、细胞和动物模型等多种研究手段，明确自噬功能抑制对矽尘所致受损线粒体清除和促炎因子分泌的作用机制；研究薯蓣皂苷促进巨噬细胞自噬的作用机制；研究薯蓣皂苷调控自噬对延缓矽肺纤维化的作用及其机制，旨在为延缓和阻抑矽肺纤维化提供新的实验和理论依据。

Silicosis is one kind of pneumoconiosis induced by inhalation of silica dust during occupational environment, which is characterized by the chronic lung inflammation and lung fibrosis. Silicosis patients consists 50 percent of the pneumoconiosis, which is the most sever and harmful occupational disease. However, the pathogenesis and the immunological modulation of silicosis are not clear yet. Our previous researches have demonstrated that the abnormal autophagy activities of alveolar macrophages in silicosis patients’ bronchoalveolar lavage fluid played a key role during the development of silicosis. And dioscin could postpone the fibrotic process by regulating autophagy. On the basis of previous work, our project will take advantage of multiple methods, such as immunology, molecular, cellular and animal model. The objective of our project is to define the mechanism of autophagy inhibition on the clearance of mitochondria and the secretion of proinflammatory cytokines; to study the role of dioscin on promoting the autophagy activity in macrophages; to demonstrate that the regulatory role and its deep mechanism of dioscin on postpone the fibrotic process by regulating autophagy. Hopefully, the novel experimental and theoretical foundation could be provided to help postponing and inhibiting the silicosis development.