临床口腔医学杂志2025，Vol.41Issue(12)：711-716,6.DOI:10.3969/j.issn.1003-1634.2025.12.003
cGAS-STING通路改善线粒体功能障碍缓解牙髓坏死根尖炎的机制
Mechanism of cGAS-STING pathway in improving mitochondrial dysfunction and alleviating pulp necrosis and apical inflammation
摘要
Abstract
Objective:To explore the mechanism of cGAS-STING pathway in improving mitochondrial dysfunction and alleviating pulp necrosis and apical inflammation.Methods:C57BL/6 mice were randomly divided into three groups:control group,model group and RU.521 group,with 6 mice in each group.Except the control group,other groups established periapical periodontitis models.After euthanasia,the right mandible was used for micro-CT scanning,and the left mandible was used for cGAS-STING pathway and mitochondrial ROS detection.Mouse bone marrow mesenchymal stem cells(BMSCs)were divided into blank group(Con),lipopolysaccharide(LPS)group,LPS+RU.521 group and LPS+RU.521+STING group.The osteogenic properties were analyzed by alkaline phosphatase(ALP)staining.The copy number of mitochondrial DNA(mtDNA)was evaluated by real-time polymerase chain reaction.Western blot analysis of cGAS-STING pathway expression.Results:Compared with the control group,the bone loss,trabecular separation(Tb.Sp)in the periapical area of the model group increased significantly,while trabecular volume fraction(BV/TV)and trabecular number(Tb.N)decreased significantly(P＜0.05).Compared with the model group,the bone loss,Tb.Sp in the periapical area of RU.521 group decreased signifi-cantly,while BV/TV and Tb.N increased significantly(P＜0.05).Compared with the control group,the percentage of cGAS positive expression in periapical area,STING positive expression and the level of MitoSOX in TOMM20 positive cells in the model group increased significantly,and the copy number of mtDNA decreased significantly(P＜0.05).Compared with the model group,the percentage of cGAS positive expression in periapical area,STING positive expression and the level of Mi-toSOX in TOMM20 positive cells in RU.521 group decreased significantly,and the copy number of mtDNA increased signifi-cantly(P＜0.05).Compared with Con group,the expression of cGAS and STING proteins and the fluorescence intensity of MitoSOX in BMSCs in LPS group increased significantly,while ALP activity and mtDNA copy number decreased significantly(P＜0.05).Compared with LPS group,the expression of cGAS,STING protein and MitoSOX fluorescence intensity in BMSCs in LPS+RU.521 group decreased significantly,while ALP activity and mtDNA copy number increased significantly(P＜0.05).In addition,STING overexpression significantly reversed the improvement of RU.521 on LPS-induced ALP activity decrease,mtDNA copy number decrease and MitoSOX fluorescence intensity increase.Conclusion:RU.521,an inhibitor of cGAS-STING pathway,can alleviate bone loss and promote osteoblast formation by mitigating local mitochondrial damage.关键词
环鸟苷酸-腺苷酸合酶/干扰素基因刺激因子/牙髓/根尖炎/线粒体Key words
Guanosine monophosphate-adenosine monophosphate synthase/Stimulator of interferon genes/Dental pulp/Apical inflammation/Mitochondria分类
医药卫生引用本文复制引用
陈莎,石婷婷,谷鑫,李少婷,于静侠,黄岩..cGAS-STING通路改善线粒体功能障碍缓解牙髓坏死根尖炎的机制[J].临床口腔医学杂志,2025,41(12):711-716,6.基金项目
2025年度河北省医学科学研究课题(20251129) （20251129）
