目的 探讨柚皮素调节GMP-AMP合成酶（cGAS）/干扰素基因刺激因子（STING）信号通路对牙周炎大鼠的治疗作用。方法 取SD大鼠通过双侧上颌第一磨牙颈部结扎法建立牙周炎模型，随机分为模型组、柚皮素50、100 mg/kg组及柚皮素100 mg/kg＋楝酰胺（RocA）0.67 mg/kg组，每组各10只，另取10只正常大鼠不做处理设为对照组。观察大鼠牙周炎症状并以Micro-CT扫描其牙槽骨，评测各组探诊深度（PD）、龈沟出血指数（SBI）、牙槽骨吸收量、骨密度、骨体积分数与骨小梁数目；以苏木精–伊红（HE）与抗酒石酸酸性磷酸酶（TRAP）染色分别检测大鼠牙周组织病理形态、炎性细胞数与牙槽骨破骨细胞数；以酶联免疫吸附测定法（ELISA）测量各组大鼠血清与牙周组织炎症因子C反应蛋白（CRP）、白细胞介素（IL）-6、IL-8水平；以免疫印迹法检测各组大鼠牙周组织cGAS/STING通路蛋白表达。结果 与对照组相比，模型组大鼠PD、SBI、牙槽骨吸收量、炎性细胞数、破骨细胞数、血清与牙周组织CRP、IL-6、IL-8水平、cGAS与STING蛋白表达显著升高，骨密度、骨体积分数与骨小梁数目显著降低（P＜0.05）；与模型组比较，柚皮素各剂量组大鼠PD、SBI、牙槽骨吸收量、炎性细胞数、破骨细胞数、血清与牙周组织CRP、IL-6、IL-8水平、cGAS与STING蛋白表达均显著降低，牙槽骨骨密度、骨体积分数与骨小梁数目均升高（P＜0.05），且呈剂量相关性。与柚皮素100 mg/kg组比较，柚皮素＋RocA组大鼠PD、SBI、牙槽骨吸收量、炎性细胞数、破骨细胞数、血清与牙周组织CRP、IL-6、IL-8水平、cGAS与STING蛋白表达显著升高，牙槽骨骨密度、骨体积分数与骨小梁数目降低（P＜0.05）。结论 柚皮素可通过减弱cGAS/STING信号活性而抑制牙周炎大鼠炎症，进而减轻其牙周组织损伤，缓解其牙槽骨骨吸收并修复其骨微结构，最终改善其临床症状。

Objective To investigate the therapeutic effect of naringenin on periodontitis in rats by regulating the cyclic GMP-AMP synthetase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Methods Periodontitis model was established by ligation of bilateral maxillary first molars in SD rats, and the rats were randomly divided into model group, naringin 50, 100 mg/kg groups, and naringin 100 mg/kg + RocA 0.67 mg/kg group, with 10 rats in each group, and 10 normal rats were selected as control group without treatment. The symptoms of periodontitis in rats were observed and their alveolar bone was scanned with Micro CT. The probing depth (PD), gingival sulcus bleeding index (SBI), alveolar bone resorption, bone density, bone volume fraction, and trabecular bone number were evaluated in each group. HE and TRAP stainings were applied to detect the pathological morphology, inflammatory cell count, and alveolar bone osteoclast count of rat periodontal tissue, respectively. Enzyme linked immunosorbent assay (ELISA) was applied to measure the levels of inflammatory factors C reactive protein (CRP), IL-8 and, IL-6 in serum and periodontal tissue of rats in each group. Immunoblotting was applied to detect the expression of cGAS/STING pathway proteins in the periodontal tissues of rats in each group. Results Compared with control group, the PD, SBI, alveolar bone resorption, inflammatory cell count, osteoclast count, serum and periodontal tissue CRP, IL-6, IL -8 levels, cGAS and STING protein expression in the model group were obviously increased, but the bone density, bone volume fraction, and number of trabeculae were obviously decreased (P < 0.05). Compared with model group, the PD, SBI, alveolar bone resorption, inflammatory cell count, osteoclast count, serum and periodontal tissue CRP, IL-6, IL-8 levels, cGAS and STING protein expression in the each dose of naringenin groups were all reduced, while the alveolar bone density, bone volume fraction, and number of trabeculae were increased (P < 0.05), and it was dose-dependent. Compared with naringenin 100 mg/kg group, naringenin + RocA group showed an increase in PD, SBI, alveolar bone resorption, inflammatory cell count, osteoclast count, serum and periodontal tissue CRP, IL-6, IL -8 levels, cGAS and STING protein expression, and a decease in alveolar bone density, bone volume fraction, and number of trabeculae (P < 0.05). Conclusion Naringenin can inhibit inflammation in periodontitis rats by reducing cGAS/STING signaling activity, thereby reducing periodontal tissue damage, alleviating alveolar bone resorption, repairing bone microstructure, and ultimately improving clinical symptoms.

R285；R988.2

福建省卫生健康委员会健康科研项目[闽卫中医函2019（202）号]