牙周炎是威胁人类健康的第三大杀手，因致病因素复杂，其具体发病机制目前尚未完全清楚。细胞焦亡(Pyroptosis)是一种依赖于GSDMD(细胞焦亡标志物)的细胞主动裂解性死亡方式，并伴随大量炎症因子释放进而导致级联炎症反应，该进程参与了多种炎症性疾病的发生与发展。文献报道牙周炎患者的牙周组织中炎症小体高表达，是否发生Pyroptosis，及其产生的作用，目前尚未有研究报道。本课题组前期研究发现牙周病患者的牙周膜中GSDMD被显著激活，且IL-1β过表达；体外模拟牙周炎致病菌感染牙周膜干细胞(PDLSCs)后，其发生大量Pyroptosis现象。鉴于此，本项目拟结合人牙周炎患者样本，建立大鼠牙周炎模型，综合运用各种生物学技术，阐明GSDMD介导的PDLSCs细胞焦亡对牙周炎发病进程的影响；同时比对细胞焦亡特异性抑制剂与临床牙周炎用药治疗效果，为临床上治疗牙周炎提供新的思路。

Periodontitis is the third leading killer of human health, due to the complex pathogenic factors, its pathogenesis has not been fully elucidated. Pyroptosis, a lytic type of cell death, is executed by GSDMD and accompanied with a large release of inflammatory cytokines. This process leads to a cascade inflammatory response and is involved in the occurrence and development of many inflammatory diseases. It is reported that inflammasome has been highly expressed in periodontal tissue of periodontitis patients. However, whether pyroptosis occurs during periodontitis and its role on periodontitis has not been reported. Our previous work indicated that GSDMD was significantly activated in the periodontal ligament of periodontitis patients and IL-1β was released in large amounts. We also found that PDLSCs showed significant pyroptosis morphology during in vitro simulated periodontal pathogen infection. Therefore, we propose a systemic solution, combining with human periodontitis samples, cultured PDLSCs, in vitro periodontal pathogen infection model, and using CRISPR/Cas-9 gene knock-out, Transwell co-culture, Cytokine array techniques to elucidate the impact of GSDMD-mediated PDLSCs pyroptosis on the pathogenesis of periodontitis. Through establishing a rat model of periodontitis, we compare the therapeutic effects of pyroptosis specific inhibitor with clinical periodontitis medications and provide new sights for clinical treatment of periodontitis by PDLSCs transplantation.