铁死亡在牙周炎中的研究进展  

Research progress on ferroptosis in periodontitis

作　　者：何毅 余东升[1] HE Yi;YU Dongsheng(Hospital of Stomatology,Guanghua School of Stomatology,Sun Yat-sen University,Guangdong Provincial Key Laboratory of Stomatology,Guangzhou 510055,China)

机构地区：[1]中山大学附属口腔医院、光华口腔医学院、广东省口腔重点实验室,广东广州510055

出　　处：《口腔疾病防治》2024年第12期963-970,共8页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金项目(82073378,82373255);广东省自然科学基金项目(2021A1515012399);广东省科技创新战略专项资金项目(pdjh2024b017)。

摘　　要：牙周炎是由菌斑微生物引起的慢性炎症性疾病,是目前导致我国成人失牙的首要原因。由于牙周炎发病机制复杂,目前发病机制仍不清楚。铁死亡(ferroptosis)是一种铁依赖性调节细胞死亡的形式,通过不同的信号途径影响细胞内谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)功能,进而抗氧化能力下降,活性氧积累,脂质过氧化,最终造成细胞和组织损伤。最近研究发现,铁超载、氧化应激和脂质过氧化与牙周炎的发生、发展过程密切相关。铁死亡主要表现为机体的氧化还原稳态被破坏,抗氧化能力降低,损伤相关的分子模式被激活,促炎介质释放,炎症被诱导或加重。铁依赖性氧化应激与脂质过氧化同时参与铁死亡与炎性疾病的调控,牙周炎致病菌能诱导牙周韧带干细胞的铁死亡,从而激活炎症因子如白细胞介素⁃17、肿瘤坏死因子⁃α、缺氧诱导因子⁃1α等的释放,加重牙周炎;另外铁死亡所激活的炎症因子在牙槽骨稳态中发挥重要作用,铁死亡参与脂多糖诱导牙龈成纤维细胞炎症的过程。未来的研究可着重于探讨铁死亡在牙周炎中作用的分子机制及其治疗靶点,为牙周病的防治提供新的策略。Periodontitis is a chronic inflammatory disease caused by plaque microorganisms,which is the main cause of tooth loss in adults in China.Due to the complexity of periodontitis,their pathogenesis is still unclear.Ferropto⁃sis is a form of iron⁃dependent regulation of cell death,which affects the function of glutathione peroxidase(GPX4)in the cell through different signaling pathways,thus decreasing antioxidant capacity,accumulation of reactive oxygen spe⁃cies and lipid peroxidation,eventually causing cell and tissue damage.Recent studies have found that iron overload,oxi⁃dative stress and lipid peroxidation are closely related to the occurrence and development of periodontitis.This article reviews the characteristics of ferroptosis and the relationship between ferroptosis and inflammatory diseases,especially periodontitis,to provide new ideas for the diagnosis,treatment,and prognosis evaluation of periodontitis.ferroptosis is mainly manifested as the disruption of the body's redox homeostasis,decreased antioxidant capacity,activation of dam⁃age related molecular patterns,release of pro⁃inflammatory mediators,and induction or exacerbation of inflammation.Iron dependent oxidative stress and lipid peroxidation are simultaneously involved in the regulation of ferroptosis and inflammatory diseases.Pathogenic bacteria of periodontitis can induce ferroptosis of periodontal ligament stem cells,there⁃by activating the release of inflammatory factors such as interleukin⁃17,tumor necrosis factor alpha,and hypoxia induc⁃ible factor⁃1 alpha,exacerbating periodontitis;In addition,inflammatory factors activated by ferroptosis play an impor⁃tant role in alveolar bone homeostasis,and ferroptosis is involved in the process of lipopolysaccharide induced inflamma⁃tion of gingival fibroblasts.Future research can focus on exploring the molecular mechanisms and therapeutic targets of ferroptosis in periodontitis,providing new strategies for the prevention and treatment of periodontal disease.

关 键 词：牙周炎 牙周韧带干细胞 铁死亡 炎症 铁代谢 铁超载 活性氧 脂质过氧化 氧化应激 糖尿病 谷胱甘肽过氧化物酶4 

分 类 号：R78[医药卫生—口腔医学]