目的 探討柚皮素調(diào)節(jié)GMP-AMP合成酶（cGAS）/干擾素基因刺激因子（STING）信號通路對牙周炎大鼠的治療作用。方法 取SD大鼠通過雙側(cè)上頜第一磨牙頸部結(jié)扎法建立牙周炎模型，隨機分為模型組、柚皮素50、100 mg/kg組及柚皮素100 mg/kg＋楝酰胺（RocA）0.67 mg/kg組，每組各10只，另取10只正常大鼠不做處理設(shè)為對照組。觀察大鼠牙周炎癥狀并以Micro-CT掃描其牙槽骨，評測各組探診深度（PD）、齦溝出血指數(shù)（SBI）、牙槽骨吸收量、骨密度、骨體積分數(shù)與骨小梁數(shù)目；以蘇木精–伊紅（HE）與抗酒石酸酸性磷酸酶（TRAP）染色分別檢測大鼠牙周組織病理形態(tài)、炎性細胞數(shù)與牙槽骨破骨細胞數(shù)；以酶聯(lián)免疫吸附測定法（ELISA）測量各組大鼠血清與牙周組織炎癥因子C反應(yīng)蛋白（CRP）、白細胞介素（IL）-6、IL-8水平；以免疫印跡法檢測各組大鼠牙周組織cGAS/STING通路蛋白表達。結(jié)果 與對照組相比，模型組大鼠PD、SBI、牙槽骨吸收量、炎性細胞數(shù)、破骨細胞數(shù)、血清與牙周組織CRP、IL-6、IL-8水平、cGAS與STING蛋白表達顯著升高，骨密度、骨體積分數(shù)與骨小梁數(shù)目顯著降低（P＜0.05）；與模型組比較，柚皮素各劑量組大鼠PD、SBI、牙槽骨吸收量、炎性細胞數(shù)、破骨細胞數(shù)、血清與牙周組織CRP、IL-6、IL-8水平、cGAS與STING蛋白表達均顯著降低，牙槽骨骨密度、骨體積分數(shù)與骨小梁數(shù)目均升高（P＜0.05），且呈劑量相關(guān)性。與柚皮素100 mg/kg組比較，柚皮素＋RocA組大鼠PD、SBI、牙槽骨吸收量、炎性細胞數(shù)、破骨細胞數(shù)、血清與牙周組織CRP、IL-6、IL-8水平、cGAS與STING蛋白表達顯著升高，牙槽骨骨密度、骨體積分數(shù)與骨小梁數(shù)目降低（P＜0.05）。結(jié)論 柚皮素可通過減弱cGAS/STING信號活性而抑制牙周炎大鼠炎癥，進而減輕其牙周組織損傷，緩解其牙槽骨骨吸收并修復(fù)其骨微結(jié)構(gòu)，最終改善其臨床癥狀。

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

福建省衛(wèi)生健康委員會健康科研項目[閩衛(wèi)中醫(yī)函2019（202）號]