慢性阻塞性肺疾病（COPD）与肺上皮细胞衰老关系密切。我们发现p97、Npl4低表达后能够明显改善COPD导致的肺上皮细胞衰老，其机制可能与SIRT1的sumo化有关。且有研究证实，去乙酰化酶SIRT1在细胞衰老中发挥至关重要的作用，而SIRT1的sumo化是影响SIRT1去乙酰化的重要原因之一。我们前期研究和现有研究报道强烈提示，p97-Npl4复合物可能通过抑制SIRT1的sumo化，进而下调SIRT1的去乙酰化活性，从而促进肺上皮细胞的衰老。为证实这一设想，本课题拟通过构建p97-Npl4低表达载体，结合COPD衰老模型的构建，观察p97-Npl4复合物对肺上皮细胞衰老的影响，并进一步探讨p97-Npl4复合物对SIRT1 sumo化及对SIRT1去乙酰化的调控作用，从而阐明p97-Npl4复合物在肺上皮细胞衰老的分子机制，为COPD提供新的药物治疗靶点。

There is a close relation between chronic pulmonary disease(COPD) and alveolar epithelial cell senescence. Our previous study showed that low expression of p97 and Npl4 can improve alveolar epithelial cell senescence induced by COPD, mechanism of which is associated with SUMOylation.And some other studies showed that SIRT1 plays vital roles in cell senescence,while SUMOylation of SIRT1 is one of the most Important causes of deacetylation effect of SIRT1.Based on our previous study and other studies, it is strongly suggested that “p97-Npl4 complex likely interpose deacetylation of SIRT1, and next regulate SIRT1 SUMOylation to anti-aging for pulmonary epithelial cell senescence”. In order to confirm this hypothesis, this project intends to observe the effect of p97-Npl4 complex on Senescence of pulmonary epithelial cells by constructing p97-Npl4 low expression vector and COPD aging model, and further explore the regulation of p97-Npl4 complex on SIRT1 sumoification and SIRT1 deacetylation, so as to elucidate the molecular mechanism of p97-Npl4 complex in senescence of pulmonary epithelial cells and provide a new way for COPD drug therapy targets.