BAFF信号在慢性牙周炎诱导肺组织损伤中的作用及机制研究

Chronic obstructive pulmonary disease(COPD) is a major global health problem and is a main cause of death and disability worldwide. Our previous studies have shown that chronic periodontitis is significantly associated with COPD, it can increase the risk of COPD and the frequency of COPD exacerbation. A high serum level of BAFF has been reported in chronic periodontitis patients. BAFF is a type II membrane protein and can induce excessive immune response, produce autoimmune injury and emphysema in lung tissue. We thus hypothesize that chronic periodontitis can increase lung tissue damage and reduce lung function by promoting the expression of BAFF in lung. In this project, we will explore the effect of chronic periodontitis on lung BAFF signal and investigate whether chronic periodontitis could affect BAFF signal and then cause pulmonary injury by constructing different animal models. At the same time, the mechanism of BAFF signal activation by periodontal pathogens will also be explored by cell culture and signal pathway blocking in vitro. With this project, we hope to further elucidate the association between chronic periodontitis and COPD, and provide new bases for COPD prevention and treatment.

慢性阻塞性肺疾病（COPD）是全球主要公共健康问题，也是世界上致死和致残的主要原因。我们前期研究显示，慢性牙周炎与COPD显著相关，其可增加COPD的患病风险和COPD急性发作频率。慢性牙周炎可促进全身BAFF信号的激活，BAFF为Ⅱ型跨膜蛋白，其高表达可诱导肺组织发生过度免疫反应，产生自身免疫性肺损伤和肺气肿的形成。因此，我们提出以下假说：慢性牙周炎可通过促进肺部BAFF表达的方式，增加肺组织破坏，降低肺功能。本研究拟在已有结论基础上，通过不同小鼠动物模型的构建，深入探讨慢性牙周炎对COPD肺部BAFF信号的影响，以及该信号在慢性牙周炎诱导肺组织过度免疫反应和肺组织损伤中的作用。同时，利用体外细胞培养和信号通路阻断的方式，探讨牙周致病菌激活机体BAFF信号的机制。我们通过该研究期望深入揭示慢性牙周炎与COPD之间的因果相关性，为COPD危险因素筛选和疾病防治提供新的理论依据。

BAFF是一种由285个氨基酸组成的Ⅱ型跨膜蛋白，可对B细胞和T细胞发挥重要的调节功能。牙周炎可诱发全身BAFF高表达，同时BAFF可诱导肺组织发生过度免疫性和自身免疫性肺组织损伤，在COPD发生和进展中发挥重要作用。然而牙周炎能否影响肺组织BAFF相关免疫反应尚不清楚。本研究通过动物模型构建、细胞培养以及相关分子生物学实验证实，牙周炎能够促进牙龈组织，外周血以及支气管灌洗液BAFF高表达。牙龈组织高表达的BAFF能够诱发牙槽骨丢失和巨噬细胞极化；肺部高表达的BAFF能够调控B细胞和T细胞免疫反应，影响实验动物肺功能。此外，牙周致病菌能够迁移至肺部，通过激活NF-κB和p38MAPK信号通路促进BAFF表达。总之，本研究以牙周炎诱导的肺组织BAFF表达为立足点，深入探讨了牙周炎对COPD肺部免疫应答反应的影响。