牙周炎是菌斑微生物与宿主免疫系统间复杂的相互作用所致的炎症性疾病。因此，牙周炎药物治疗应从调控病原微生物与宿主免疫系统间相互作用入手。已有研究表明，toll样受体4（TLR4）在牙周炎患者牙周组织中高表达，且TLR4能够与细菌脂多糖结合，启动固有免疫应答。黄连素作为TLR4拮抗剂能够抑制固有免疫过激应答造成的炎症反应；并通过调控成骨/破骨细胞功能有望改善组织破坏。此外，水凝胶能更好的充盈到缺损的各个位点，并通过缓释维持药物局部浓度。为此，本研究以水凝胶为载体与黄连素复合，采用细胞生物学和分子生物学手段研究其对固有免疫细胞TLR4通路的调控作用，明确其在牙周炎中通过TLR4通路调控成骨/破骨细胞功能的作用机制；建立TLR4-/-小鼠牙周炎模型，通过micro-CT和组织学验证该体系以TLR4为靶点，调控固有免疫应答治疗牙周炎的作用，从而为牙周炎的药物治疗提供新靶点，具有较好研究前景。

Periodontitis is an inflammatory disease caused by the complex interaction between plaque microorganisms and the host immune system. Therefore, periodontitis drug therapy should be designed by regulating the interaction between pathogenic microorganisms and the host immune system. Previous studies have shown that toll-like receptor 4 (TLR4) is highly expressed in periodontal tissues of patients with periodontitis, and TLR4 can bind to bacterial lipopolysaccharide, initiate an innate immune response, and cause an inflammatory response. Berberine as a TLR4 antagonist can inhibit the inflammatory response caused by the innate immune overreaction; and it is expected to improve tissue destruction by regulating osteogenesis/osteoclast function. In view of the limitations of periodontal tissue defect irregularity, the application of temperature-sensitive hydrogel can better fill the various sites of the defect and maintain the local concentration of the drug through sustained release. To this end, this project will use hydrogel as a carrier to complex with berberine, and take cell biology and molecular biology to study its regulation of the innate immune cell TLR4 pathway, to clarify its regulation of osteogenesis/breaking through TLR4 pathway in periodontitis, and to reveal mechanism of action of osteocyte function. Through establishing TLR4-/- mouse periodontitis model, micro-CT and histology are used to verify that the system targets TLR4 and regulate the role of innate immune response in the treatment of periodontitis. This study provides new opinions and methods for the treatment of periodontitis, and has great potential research prospects and application value.