铁死亡在牙周炎发生发展过程中的研究进展  

Research progress of ferroptosis in the occurrence and development of periodontitis

作　　者：孙瑞蔓 秦旭 朱光勋 SUN Ruiman;QIN Xu;ZHU Guangxun(Department of Stomatology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;School of Stomatology,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院口腔科,湖北武汉430030 [2]华中科技大学同济医学院口腔医学院,湖北武汉430030 [3]口腔颌面发育与再生湖北省重点实验室,湖北武汉430030

出　　处：《口腔疾病防治》2025年第4期336-343,共8页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：湖北省自然科学基金(2023AFB653,2023AFB765)。

摘　　要：牙周炎是以牙周组织持续的炎症反应和进行性破坏为主要特征的慢性感染性疾病。铁死亡是一种可调控的,具有铁依赖性的新型程序性细胞死亡形式,在多种疾病中发挥着重要作用,其主要特征为铁代谢异常、抗氧化防御减弱以及脂质过氧化物堆积。近年来,越来越多的研究表明铁死亡与牙周炎发生、发展存在相关性。目前报道的发生于牙周膜成纤维细胞、牙周膜干细胞、人类永生化口腔上皮细胞、人牙龈成纤维细胞、牙髓干细胞、MLOY4骨细胞、小鼠下颌骨成骨细胞和巨噬细胞的铁死亡相关文献结果表明,牙周炎中广泛存在铁死亡现象。这一现象主要与铁离子代谢、脂质代谢、胱氨酸/谷氨酸逆向转运蛋白(cystine/glutamate antiportersystem,systemxc-)/谷胱甘肽(glutathione,GSH)/谷胱甘肽过氧化物酶4(glutathioneperoxidase4,GPX4)、烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)/铁死亡抑制蛋白1(ferroptosis suppressor protein 1,FSP1)/辅酶Q10(coenzyme Q10,CoQ10)、kelch样环氧氯丙烷相关蛋白-1(kelchlike ECH-associated protein-1,Keap1)/核因子E2相关因子2(nuclear factor erythroid2-related factor 2,NRF2)和p53等途径有关。目前研究表明,铁死亡在调节牙周软、硬组织破坏,炎症反应以及牙周病原菌参与全身性疾病进展中发挥了重要作用。尽管目前铁死亡在牙周炎中的作用机制有较多研究,但在牙周治疗的应用方面尚存在许多不确定性,相关药物仍需进一步开发探索。Periodontal disease is a chronic infectious disease characterized by chronic inflammation and progressive destruction of the periodontal tissue.Ferroptosis,an iron-dependent form of programmed cell death,is primarily characterized by altered iron homeostasis,weak antioxidant defense,and accumulation of lipid peroxides and plays an important role in a variety of diseases.Recent research has shown the correlation between ferroptosis and the occurrence and development of periodontal disease.Through in-depth research of relevant literature on periodontal ligament fibroblasts,periodontal ligament stem cells,human immortalized oral epithelial cells,human gingival fibroblasts,dental pulp stem cells,MLOY4 cells,mouse mandibular osteoblast,and macrophages,we found that ferroptosis is widely suppressed in periodontal disease.This phenomenon is primarily related to lipid metabolism,iron metabolism,cysteine/glutamate transporter system xc⁃/glutathione/glutathione peroxidase 4,nicotinamide adenine dinucleotide phosphate/ferroptosis sup⁃pressor protein 1/coenzyme Q10,kelch⁃like ECH⁃associated protein⁃1/nuclear factor E2 related factor 2,and p53.Cur⁃rent research indicates that ferroptosis plays an important role in regulating the destruction of periodontal soft and hard tissues,inflammatory response,and periodontopathogen⁃induced progression of systemic diseases.Although there are several studies on the mechanism of ferroptosis in periodontal disease,there are many uncertainties in the application of ferroptosis in periodontal therapy.Therefore,further studies are required to explore and develop ferroptosis⁃related drugs for the treatment of periodontal disease.

关 键 词：牙周炎 铁死亡 活性氧 炎症反应 全身性疾病 牙周病原菌 铁离子代谢 脂质代谢 氨基酸抗氧化系统 谷胱甘肽过氧化物酶4 铁死亡抑制蛋白1 

分 类 号：R78[医药卫生—口腔医学]