健脾益肺II号临床防治COPD作用较好，但生物学机制并不清楚。前期研究提示健脾益肺II号能够降低COPD大鼠血清中MDA水平、提高SOD与GSH活性表明其具有较好的抗氧化损伤作用。其机制可能与增强Sirt1表达、增强FOXO3/p53信号通路抑制衰老相关，但需进一步验证。因此，本项目拟通过烟雾感染建立大鼠COPD模型，以Sirt1/FOXO3/p53信号通路为靶点，研究烟雾感染氧化应激对COPD衰老影响及健脾益肺II号抗COPD氧化应激的作用及其机制。拟在COPD大鼠模型上，采用Sirt1基因敲除及基因过表达技术确证Sirt1在COPD氧化衰老中的作用，检测衰老指标变化、蛋白与脂质氧化、FOXO3和p53蛋白表达变化。

JianPiYifei II formula has good effect in the prevention and treatment of chronic obstructive pulmonary disease (COPD) in clinic, but the biological mechanism is not clear. Previous studies have demonstrated that JianPiYifei II formula can decrease MDA content and increase SOD activity in plasma of COPD rats, which means that JianPiYifei II formula has anti-oxidative effect. The mechanisms may be related with the increase of Sirt1 expression and FOXO3/p53 pathway so as to the inhibition of senescence. To test the hypothesis, cigarette smoke-induced rat COPD disease models will be utilized. We will target Sirt1/FOXO3/p53 signaling pathway to explore the effects of JianPiYifei II formula on senescence of COPD and its related mechanisms. In COPD rat model, using Sirt1 gene knockout and overexpression to confirm the role of Sirt1 in the senescence of COPD. Moreover, we will further investigate the senescence markers, protein and lipids oxidation, FOXO3 and p53 protein expressions in Sirt1 gene knockout and overexpression rats.