一氧化碳(CO)在细胞和组织损伤模型中具有抗炎症、抗氧化和抗凋亡作用。然而，CO是否具有抗衰老作用尚未阐明。前期研究发现，CO通过整合性应激反应(ISR)可诱导应激颗粒(SG)的形成，而SG可包裹Ⅰ型纤溶酶原激活物抑制因子(PAI-1)；PAI-1在介导细胞衰老参与特发性肺纤维化发病的分子机制中起到关键作用。由此设想，CO诱导产生的SG可能通过包裹PAI-1减缓细胞衰老，从而抑制肺纤维化的形成。本研究用依托泊苷和细胞传代培养方法分别建立DNA损伤和复制性衰老模型；用ISR抑制剂、免疫荧光染色和免疫共沉淀法，探讨CO诱导产生的SG是否通过包裹PAI-1减缓细胞衰老；用依托泊苷或博莱霉素建立特发性肺纤维化模型，探讨CO是否通过产生SG抑制肺纤维化的形成。本研究将首次揭示CO通过ISR诱导产生的SG对细胞衰老参与肺纤维化形成的干预机制，为利用外源性CO预防与治疗特发性肺纤维化提供实验依据。

Carbon monoxide (CO) possesses anti-inflammatory, anti-oxidant and anti-apoptotic properties in a variety of cellular- and tissue-injury models. However, whether CO exerts anti-senescence effects is not well defined. Our recent study showed that CO can induce stress granule (SG) formation through integrated stress response (ISR). Additionally, SG can sequestrate plasminogen activator inhibitor-1 (PAI-1), which exhibits an essential role in the cellular senescence-mediated pulmonary fibrosis. Based on these reports, we hypothesized that CO-induced SG might suppress cellular senescence and pulmonary fibrosis via sequestration of PAI-1. Human diploid lung fibroblasts and type II alveolar epithelial cells were applied to establish DNA damage and replicative cellular senescence. ISR inhibitor was used to identify whether CO-induced SG formation can delay the cellular senescence through PAI-1 sequestration. Next, to verify whether SG assembly is involved in prevention of pulmonary fibrosis, we constructed idiopathic pulmonary fibrosis model by oropharyngeal instillation of etoposide and bleomycin. This study is the first one to demonstrate that CO can inhibit cellular senescence and pulmonary fibrosis via induction of SG assembly, and which provides important experimental and clinical application prospects on treatment of idiopathic pulmonary fibrosis.