具核梭杆菌通过NLRX1/ROS/NLRP3炎性小体途径促进慢性牙周炎发展的机制研究

具核梭杆菌（F. nucleatum）作为重要的牙周致病菌，能通过诱发宿主免疫反应加重牙周支持组织破坏，其引起的免疫破坏作用明显强于其它公认的牙周致病菌。最新研究表明，慢性牙周炎患者牙龈组织及龈沟液中NLRP3含量显著升高，NLRP3炎性小体是机体固有免疫的主要构成部分，能被活性氧（ROS）激活，在牙周炎中的作用尚不明确。线粒体内的NLRX1能直接调控ROS的产生。申请人前期研究证实F. nucleatum能显著促进牙龈细胞内ROS的产生，然而，ROS产生的机制及是否受到NLRX1调控尚不明确，F. nucleatum引起的ROS产生对牙周组织内NLRP3炎性小体的激活及牙周支持组织破坏的影响尚未有明确报道。因此，本课题拟在前期工作基础上，通过体内外实验从不同角度验证F. nucleatum是否通过调控NLRX1的表达，促进ROS的产生进而激活NLRP3炎性小体，加重慢性牙周炎发展。

F. nucleatum, as an important periodontal pathogen, can aggravate periodontal tissue destruction by inducing host immune response and the immune damage induced by it was obviously stronger than other recognized periodontal pathogens. Current studies have shown that the level of NLRP3 in gingival tissue and gingival crevicular fluid is significantly increased in patients with chronic periodontitis. As a major component of innate immunity, NLRP3 inflammasome can be significantly activated by reactive oxygen species (ROS) and the role of NLRP3 inflammasome in the development of periodontitis is still unclear. NLRX1 located in mitochondria can directly promote the production of ROS. Our previous study had confirmed that F. nucleatum could significantly promote the ROS generation in GFs, however, the mechanism of ROS generation and whether it is regulated by NLRX1 remain unclear; in addition, the effect of F. nucleatum induced ROS production on NLRP3 inflammasome activation in periodontal tissues and the destruction of periodontal supporting tissues has not been clearly clarified. Therefore, based on our previous study, this project aims to further verify whether F. nucleatum promotes the ROS generation by regulating NLRX1 expression and then activates NLRP3 inflammasome, and thus aggravates the development of chronic periodontitis through in vitro and in vivo experiments.