M1巨噬细胞与骨破坏密切相关，P.gingivalis是根尖周炎发生的主要致病菌，可促进巨噬细胞M1极化，但具体机制不明。文献研究表明P.gingivalis促进IL-6表达，且IL-6/STAT3/Hepcidin通路参与巨噬细胞铁代谢调控；申请人前期研究发现铁代谢与巨噬细胞极化密切相关。因此推测IL-6/STAT3/Hepcidin通路激活可能是P.gingivalis促进巨噬细胞M1极化进而导致根尖周炎性骨病损的关键机制。本项目拟通过动物模型、慢病毒转染、RNA-seq等技术，探讨IL-6/STAT3/Hepcidin通路调控巨噬细胞M1极化，参与P.gingivalis导致根尖周炎骨组织破坏的作用及其机制；并通过干预该通路表达，体外细胞共培养、动物模型探讨其重塑根尖周骨稳态的机制。预期将从免疫代谢新视角揭示根尖周炎骨病损发生发展的机制，为慢性根尖周炎骨破坏的治疗提供新思路。

M1 macrophages play a crucial role in bone destruction. P.gingivalis which is the main pathogen causing apical periodontitis can promote M1 polarization of macrophages, but the specific mechanism remains unclear. Recent studies showed that P.gingivalis promotes the expression of IL-6 and the IL-6/STAT3/Hepcidin pathway is involved in the iron metabolism regulation of macrophages. Previously, the applicant found that iron metabolism was closely related to macrophage polarization. Therefore, it’s reasonable to propose a hypothesis that the activation of the IL-6/STAT3/Hepcidin pathway may be the key mechanism for P.gingivalis to promote M1 macrophages polarization and lead to the development of apical inflammatory bone destruction. To validate this hypothesis, animal model, lentivirus transfection and RNA-seq et al. technologies will be used to investigate the role and mechanism of IL-6/STAT3/Hepcidin pathway in regulating macrophage M1 polarization involved in P.gingivalis causing periapical bone destruction. Furthermore, in vitro co-culture models of osteogenic/osteoclastic precursors and macrophages managed with IL-6/STAT3/Hepcidin pathway inhibitors will be constructed to evaluate its regulatory mechanism on remodeling local bone metabolism by regulating macrophage polarization, and animal experiments will be conducted to verify this regulatory mechanism in vivo. This study is expected to reveal the occurrence and development mechanisms of chronic apical inflammation as well as alveolar bone resorption induced by P.gingivalis from a new perspective of immune metabolism. Moreover, this study will provide a theoretical basis for new treatment strategy of chronic apical inflammation through immune regulation.