NLPR3炎症小体在粪肠球菌导致根尖周炎复发中的作用和机制探讨

Pulpitis and periapical periodontitis is one of the most common diseases in the dental clinics, and root canal therapy is the first choice for the treatment. Enterococcus faecalis is the most commonly detected species in the root canals of endodontic failure cases. In our previous experiments, we found that E.faecalis were able to survive in high alkaline, oligotrophic stress conditions, and invade deep dentine tubules,so it may cause the persistent infection of root canals. In order to further clarify the relationship between E.faecalis and the recurrence of periapical periodontitis, we first investigated the proinflammatory ability of E.faecalis，and found that E.faecalis induced IL-1β secretion, Caspase-1 and NLRP3 activation in THP-1 macrophages. We also found NLRP3 were up-regulated in periapical lessions. Therefore, this project aims to further clarify the role and molecular regulation mechanism of NLRP3 in the secretion of inflammatory factor IL-1β induced by E.faecalis, this may provide new ideas for finding root canal disinfection or root canal filling new drugs, and build a foundation for improving the success rate of root canal treatment.

牙髓炎和根尖周炎是我们口腔门诊上最常见的疾病之一，而根管治疗术是目前临床上牙髓病和根尖周疾病的首选治疗方法，粪肠球菌是根管治疗失败病例根管内最常检出的细菌。我们前期研究发现粪肠球菌能够耐受高碱性、寡营养环境及入侵牙本质小管深处，长期存活于充填后的根管，成为根管持续性感染的隐患。为了进一步明确粪肠球菌与根尖周炎复发的关系，我们首先检测了粪肠球菌的促炎能力。通过预初实验发现粪肠球菌能够促进THP-1巨噬细胞IL-1β的分泌及Caspase-1和NLRP3的活化。而且进一步检测临床根尖周炎病损组织样本也发现NLRP3炎症小体的表达显著增加。因此，本项目拟通过实验进一步明确NLRP3在粪肠球菌促进炎症因子IL-1β分泌中的作用和其分子调控机制，为寻找根管消毒或根管充填新药物提供新思路，为临床改善根管治疗措施、提高根管治疗成功率提供研究基础。

牙髓炎和根尖周炎是我们口腔门诊上最常见的疾病之一，而根管治疗术是目前临床上牙髓病和根尖周疾病的首选治疗方法，粪肠球菌是治疗失败根管内最常检出的细菌。我们前期实验发现粪肠球菌能够耐受高碱性、寡营养环境及入侵牙本质小管深处，长期存活于充填后的根管。为了进一步明确粪肠球菌与根尖周炎复发的关系，我们检测了粪肠球菌的促炎能力。通过本研究发现粪肠球菌通过活化caspase-1和NLRP3炎症小体来诱导细胞焦亡和IL-1β分泌，同时明确了NLRP3炎症小体活化依赖K+流出和P2X7R，而且ROS释放及自噬也参与调控NLRP3活化和IL-1β分泌。本研究为探讨粪肠球菌导致根尖周炎复发机制提供了基础，NLRP3炎症小体可能是预防粪肠球菌导致的根尖周炎复发潜在因子。