Periodontitis is an oral chronic inflammatory disease. Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis. Metformin not only has hypoglycemic effect but also has anti-inflammatory effect. Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway. High mobility group box 1 (HMGB1) has been implicated in the pathogenesis of many inflammatory diseases including periodontitis, it can participate in the induction of oxidative stress. HMGB1 is an autophagy regulator under oxidative stress, which can activate mTOR pathway. However, it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis. Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8, real-time PCR and enzyme-linked immunosorbent assay. Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro. Experimental periodontitis mice model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo. The results of CCK-8, real-time PCR, enzyme-linked immunosorbent assay, Western blot and immunofluorescence showed lipopolysaccharide (LPS) treatment inhibited cell viability, and increased HMGB1 expression at a dose-independent manner. Metformin can reduce the effect of LPS. It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression. In addition, metformin attenuated alveolar bone resorption induced by ligation. This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention.

牙周炎是一种口腔慢性炎症性疾病。抑制组织破坏、促进组织再生是治疗牙周炎的重要手段。二甲双胍不仅有降血糖作用，还有抗炎作用。二甲双胍已被证明可抑制氧化应激并通过 AMPK/mTOR 通路激活自噬。高迁移率族盒 1 (HMGB1) 与包括牙周炎在内的许多炎症性疾病的发病机制有关，它可以参与氧化应激的诱导。HMGB1是氧化应激下的自噬调节因子，可激活mTOR通路。但二甲双胍是否与HMGB1相关及其在牙周炎过程中的机制尚不清楚。通过 Cell Counting Kit-8 阐明细胞活力和炎性细胞因子的表达，实时 PCR 和酶联免疫吸附测定。进行蛋白质印迹和免疫荧光以确定 HMGB1 细胞内定位和自噬相关蛋白的表达体外。通过施用结扎线诱导实验性牙周炎小鼠模型。免疫组化检测HMGB1在体内的表达和定位。CCK-8、实时荧光定量 PCR、酶联免疫吸附测定、Western blot 和免疫荧光的结果显示脂多糖 (LPS) 处理抑制细胞活力，并以剂量​​依赖性方式增加 HMGB1 表达。二甲双胍可降低 LPS 的作用。它还可以改善 LPS 抑制的自噬途径并下调 mTOR 表达。此外，二甲双胍可减轻结扎引起的牙槽骨吸收。该研究为二甲双胍是治疗牙周炎的潜在药物和HMGB1可能是牙周干预的潜在靶点提供了新的证据。