矽肺是尘肺中最常见且危害最严重的一种疾病。自噬作为可选择性的细胞死亡方式与凋亡密切相关，被认为是矽肺潜在的发病机制。我们前期研究发现矽肺患者肺泡巨噬细胞（alveolar macrophage，AM）自噬体增多，p62/sequestosome1 (SQSTM1) 蛋白表达增高导致 AM自噬降解障碍，并加重AM凋亡，同时发现矽肺患者血清中p62表达增高。p62依赖的选择性自噬在矽肺的发病进程中可能起着重要的作用。本项研究通过建立小鼠矽肺模型，观察p62依赖的选择性自噬对矽肺病理过程的影响，确定矽肺病理进程中p62对细胞凋亡和炎症因子的调控作用，分析p62依赖的选择性自噬对矽肺发生发展的影响。同时观察抑制p62对矽肺纤维化的治疗作用，进一步明确p62依赖的选择性自噬和矽肺纤维化的相互调控关系，探寻自噬抗矽肺纤维化作用的新靶标。以期为延缓和阻抑肺纤维化发生发展提供新的实验和理论依据。

Silicosis is one of the most common and serious types of pneumoconiosis. Autophagy as an alternative cell death pathway is closely linked with apoptosis. Autophagy is considered as the potential pathogenesis of silicosis. Our previous study found that autophagosomes were increased in alveolar macrophage (AM) of human silicosis. The increased p62/sequestosome1 (SQSTM1) protein led to defect of autophagic degradation and exacerbated the apoptosis of AM. We also found that p62 was increased in silicotic patients’ serum, p62-dependent type of selective autophagy may play an important role in the progression of silicosis. This study establish silicotic mice model to observe the influence of p62-dependent type of selective autophagy in the pathological progression of silicosis, and determine the regulatory effect of p62 on apoptosis and inflammation in the pathological progression of silicosis. Analyze the influence of p62-dependent type of selective autophagy on the development of silicosis. Meanwhile, this study observes the effect of p62 inhibition on treatment of silicosis, and make more explicit of mutual regulation between p62-dependent type of selective autophagy and silicotic fibrosis. The purpose is to search the new target of autophagy against silicotic fibrosis, and clarify the mechanism about it. This study may provide new experimental and theoretical basis to delay and obstruct the development of pulmonary fibrosis.