Klotho是近年来发现的一种抗衰老蛋白。研究表明该蛋白与小鼠老年性肺气肿形成密切相关，且具有抗炎、抗氧化应激等作用。项目组前期结果表明慢性阻塞性肺气肿患者肺组织klotho表达水平明显降低，且肺组织klotho主要分布于支气管上皮细胞；通过体外实验证实，支气管上皮细胞klotho的表达能够抑制慢性阻塞性肺气肿相关细胞的炎症因子、氧化应激及蛋白酶表达。本研究拟进一步从临床－动物模型－细胞水平， 分别采用染色质免疫共沉淀、siRNA干扰、定量PCR等相关技术，明确香烟等有害因素对支气管上皮细胞klotho表达的影响，并进一步了解其在慢性阻塞性肺气肿形成中的作用及机理。本项目的实施可望揭示慢性阻塞性肺气肿形成的新机制，对于探索COPD治疗的新途径具有重要意义。

Klotho(KL) is a newly discovered anti-aging protein, which has been shown to play an important role in the formation of senile emphysema, and it has various functions, including anti-inflammation, anti-oxidative stress. We found that klotho expression in lung tissue is much lower in obstructive pulmonary emphysema patients than in control group, while KL expression is mainly in airway epithelial cells. And in vitro, KL expression by epithelial cells has been shown to inhibit the inflammatory cytokines release，oxidative stress as well as the proteolytic enzymes by inflammatory cells. In this study, chormain immunoprecipitation, siRNA interference and real time PCR will be employed to investigate the effects of pathogenetic factors such as cigarette smoking, on expression of KL by airway epithelial cells. And we also further explore the role of KL by epithelial cells in chronic obstructive ephysema. The results might reveal the novel mechanism of the emphysema and be helpful in exploring the new treatments of COPD.