慢性阻塞性肺疾病（慢阻肺）是一种与衰老相关的慢性疾病。我们前期研究并报道了肺上皮细胞衰老是肺衰老的重要表现。β2-微球蛋白（B2M）是组织相容性复合物Ⅰ类抗原（或人类白细胞抗原）的轻链亚单位组份，近期研究提示其也是一种系统性的致衰老因子。在此，我们假设B2M通过诱导肺上皮细胞衰老参与慢阻肺的发生发展。为了验证假说，首先观察慢阻肺患者的外周血及肺上皮细胞是否存在高表达的B2M，且与疾病的严重程度相关；利用小鼠慢性烟雾暴露模型，动态观察肺上皮细胞B2M表达水平与肺脏病理改变间的关系以及B2M腺病毒慢性转染能否加速肺气肿的发展；借助人原代肺上皮细胞培养进一步验证B2M可以通过相关分子信号通道诱导肺上皮细胞衰老，促进其异常炎症因子表达、黏液高分泌、减弱其增殖修复能力而参与慢阻肺的发生发展。该项目的实施将有助于丰富对慢阻肺发病机制的认识，探寻新的治疗靶点。

Chronic obstructive pulmonary disease (COPD) is a chronic disease associated with senescence. We have previously shown that senescence in lung epithelial cells is an important feature of lung aging. β2-microglobulin（B2M）is a small light chain expressed as a subunit of the histocompatibility complex classⅠantigen (also defined as human leukocyte antigen). Recent studies suggest that B2M may act as a systemic pro-aging factor. Herein, we hypothesize that B2M participates in occurrence and development of COPD through inducing senescence of lung epithelial cells. To address this, we will measure the expression of B2M in peripheral blood and lung epithelial cells of COPD patients compared with the controls, and analyze the relationships between the expression of B2M and lung function. Using a murine model of chronic exposure to cigarette-smoke, the relationships between the expression of B2M and pathological changes of lung will be observed at different time points. Furthermore, we will observe whether chronic B2M-adenovirus transfection accelerates the development of emphysema in murine lungs. Finally, using primary human lung epithelial cell culture, the effects of B2M on senescence of lung epithelial cells, abnormal expression of inflammatory cytokines, mucus hypersecretion, impaired ability of regeneration and repairing and the epithelial-mesenchymal transition will be further studied. We believe that the present study will contribute to enrich the pathogenisis of COPD, and benefit for innovative treatment of COPD.