牙周炎发病率高、危害大，而氧化应激介导的组织破坏及炎症反应是牙周炎发生发展的重要病理机制之一，但其确切机理未见阐明。课题组研究证实：线粒体功能障碍在牙周炎组织破坏中起重要作用，而线粒体分裂蛋白Drp1介导的线粒体功能障碍是诱发氧化应激破坏效应的关键因素；同时Drp1与牙周炎炎症反应关键调控因子（NLRP3炎症小体）的活化密切相关。然而，Drp1对牙周炎氧化应激反应的确切调节作用及Drp1的分子调控机制尚不清楚。本研究拟构建人牙周膜细胞损伤及炎症模型，采用化学及基因手段正反双重探究Drp1在细胞损伤及NLRP3炎症小体活化中的调控作用；利用基因芯片、Pull-down联合质谱分析等技术从基因及蛋白水平全面阐明Drp1的调控机制；联合牙周炎动物模型，应用抑制剂及基因敲除小鼠，最终验证Drp1的调控作用及分子机制。本研究不但为牙周炎病理发生提供新的分子机制，而且为其防治提供新策略与新靶点。

Periodontitis, a highly prevalent disease, results in massive costs to the patients as well as the whole society. Oxidative stress induced tissue injury and inflammatory response were recognized as a crucial pathogenesis in the development and progression of periodontitis. However, the underlying mechanisms are not well understood. Our previous studies revealed that mitochondrial dysfunction played a crucial role in the destruction of periodontal tissues. Mitochondrial dysfunction mediated by dynamin-related protein 1 (Drp1), a key mitochondrial fission protein, represented an important pathological factor of oxidative stress damage. Furthermore, Drp1 was proved to be closely associated with the activation of NLRP3 inflammasome, a master regulator of periodontal inflammation. However, the specific regulating effect of Drp1 on periodontal oxidative stress response and related mechanisms remain elusive. In this proposal, we will establish injury and inflammatory model of human periodontal ligament cells to unveil the role of Drp1 in periodontal tissue destruction and activation of NLRP3 inflammasome with chemical and genetic approaches. We will further identify the regulatory mechanism of Drp1 at protein and gene level using gene chip technology, pull-down assay as well as other molecular biological detection methods. Ultimately, we will verify the regulating effect of Drp1 and related mechanism by adopting periodontitis animal model with inhibitor used and gene knock-out mice. This comprehensive study will not only provide new insights into the pathological mechanism of periodontitis, but also make a solid foundation for the development of new therapeutic strategies and targets in the prevention or treatment of periodontitis.