铁死亡在2型糖尿病性骨质疏松症中的作用机制和研究进展  

Pathogenesis and advancements of ferroptosis in type 2 diabetic osteoporosis

作　　者：郭曼 黄炜 伍棋 曾艳 滕方元 徐勇 GUO Man;HUANG Wei;WU Qi;ZENG Yan;TENG Fang-yuan;XU Yong(Department of Endocrinology and Metabolism,Metabolic Vascular Disease Key Laboratory of Sichuan Province,Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan,China;Department of Pathology,Precision Pathology Diagnosis for Serious Diseases Key Laboratory of Luzhou,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan,China)

机构地区：[1]西南医科大学附属医院内分泌与代谢科,代谢性血管疾病四川省重点实验室,代谢性血管疾病川渝共建重点实验室,四川泸州646000 [2]西南医科大学附属医院病理科,重大疾病精准病理诊断泸州市重点实验室,四川泸州646000

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2024年第5期498-505,共8页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金(U22A20286、82300911、32201056、82170834)。

摘　　要：2型糖尿病性骨质疏松症(type 2 diabetic osteoporosis,T2DOP)是老年糖尿病患者常见的严重并发症之一。骨细胞和成骨细胞异常死亡,将造成骨形成与骨吸收代谢失衡,进而降低骨密度和增加骨折风险。铁死亡是一种铁依赖性的、脂质过氧化引起的调节性细胞死亡模式,细胞内二价铁离子(Fe 2+)通过氧化还原反应产生大量铁依赖性活性氧,促使脂质过氧化导致细胞死亡。目前,铁死亡在T2DOP发生发展中的作用与详细机制尚未完全阐明。铁死亡可能通过谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、铁超载和脂质过氧化等途径加速T2DOP疾病进展,本综述基于铁死亡理论进一步探讨T2DOP的发病机制和潜在治疗靶点,以期为T2DOP诊疗及药物研发提供新策略和方向。Type 2 diabetic osteoporosis(T2DOP)is a common and serious complication in elderly patients with diabetes.Abnormal death of osteocytes and osteoblasts leads to an imbalance between bone formation and resorption,resulting in reduced bone mineral density and increased risk of fractures.Ferroptosis is a type of iron-dependent regulated cell death induced by lipid peroxidation.Intracellular ferrous ions(Fe 2+)generate iron-dependent reactive oxygen species through oxidation-reduction reactions,promoting lipid peroxidation and leading to cell death.Currently,the role and detailed mechanisms of ferroptosis in the development of T2DOP remain unclear.In this article,how ferroptosis may accelerate the progression of T2DOP through pathways involving glutathione peroxidase 4(GPX4),iron overload and lipid peroxidation was summarized,and the pathogenesis and potential therapeutic targets of T2DOP based on ferroptosis theory were further explored,hoping to provide new strategies and directions for the diagnosis,treatment and drug development of T2DOP.

关 键 词：2型糖尿病 高血糖 骨质疏松症 铁死亡 发病机制 

分 类 号：R5[医药卫生—内科学]