AZGP1调控牙周膜干细胞焦亡在伴2型糖尿病牙周炎中的作用及机制研究

伴2型糖尿病牙周炎以加剧的炎症反应、更显著的牙周组织破坏为特点。糖代谢相关分泌因子如何调控牙周炎症及组织再生是该疾病的研究短板。AZGP1是调节糖代谢及炎症的重要分泌蛋白之一。申请者前期发现AZGP1在伴2型糖尿病牙周炎患者的牙周组织中表达增加，在人原代牙周膜干细胞中过表达AZGP1后降低了LPS和高糖刺激下炎症因子TNFα，IL-1β和IL-6的表达，抑制了焦亡关键效应蛋白Caspase-1 p20和N-GSDMD表达。推测AZGP1可通过调节焦亡抑制牙周组织炎症，减轻牙槽骨丢失，但其中AZGP1作用的具体机制不明。因此，本项目拟采用在AZGP1-/-小鼠上进行牙周炎和2型糖尿病造模，结合体外人原代牙周膜干细胞AZGP1过表达或敲低，Caspase-1抑制剂抑制焦亡，探索在伴2型糖尿病牙周炎中，AZGP1调控焦亡在其中的作用和具体机制，完善糖代谢相关分泌因子对牙周炎调控的机制网络图。

Periodontitis with type 2 diabetes mellitus(T2DM) is characterized by increased inflammatory response and significant destruction of periodontal tissue. There still lack exploration of the way glucose metabolism related secretory factors regulate periodontal inflammation and tissue regeneration. AZGP1 is one of the important secretory protein that regulate systemic glucose metabolism and inflammation. We found that AZGP1 expression was increased in patients with periodontitis+T2DM. Moreover, overexpression of AZGP1 in human periodontal ligament stem cells(hPDLSCs) inhibited the expression of inflammatory factors IL-6, IL-1β, TNFα, and effector proteins of pyroptosis (Caspase-1 p20 and N-GSDMD) in respond to LPS+high glucose. Therefore, we hypothesized that AZGP1 could inhibit inflammatory signaling in periodontal through regulating pyroptosis, thus reducing periodontal inflammation and alveolar bone loss. However, the specific mechanisms of AZGP1 in regulating pyroptosis and inflammation is unknown. Therefore, AZGP1-/- mice, hPDLSCs, Caspase-1 inhibitors and AZGP1 overexpression or knockdown techniques are to be used to explore the effects and mechanisms of AZGP1 in regulating pyroptosis of hPDLSCs on periodontitis with T2DM, and to improve the mechanism’s diagram of glucose metabolism related secretory factors on periodontitis.