Feng Jiawei, Wang Jialin, Wang Yuqing, Huang Xiaoting, Shao Tengteng, Deng Xiaofei, Cao Yemin, Zhou Mingmei, Zhao Cheng
Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Cell Dev Biol. 2022 Jul 8;10:898657. doi: 10.3389/fcell.2022.898657. eCollection 2022.
Diabetic ulcers are one of the major complications of diabetes, and patients usually suffer from amputation and death due to delayed ulcer wound healing. Persistent inflammation and oxidative stress at the wound site are the main manifestations of delayed wound healing in diabetic ulcers. In addition, chronic hyperglycemia in patients can lead to circulatory accumulation of lipid peroxidation products and impaired iron metabolism pathways leading to the presence of multiple free irons in plasma. Ferroptosis, a newly discovered form of cell death, is characterized by intracellular iron overload and accumulation of iron-dependent lipid peroxides. These indicate that ferroptosis is one of the potential mechanisms of delayed wound healing in diabetic ulcers and will hopefully be a novel therapeutic target for delayed wound healing in diabetic patients. This review explored the pathogenesis of diabetic ulcer wound healing, reveals that oxidative stress and lipid peroxidation are common pathological mechanisms of ferroptosis and delayed wound healing in diabetic ulcers. Based on strong evidence, it is speculated that ferroptosis and diabetic ulcers are closely related, and have value of in-depth research. We attempted to clarify prospective associations between ferroptosis and diabetic ulcers in terms of GPX4, iron overload, ferroptosis inhibitors, AGEs, and HO-1, to provide new ideas for exploring the clinical treatment of diabetic ulcers.
糖尿病溃疡是糖尿病的主要并发症之一，患者常因溃疡伤口愈合延迟而面临截肢和死亡。伤口部位持续的炎症和氧化应激是糖尿病溃疡伤口愈合延迟的主要表现。此外，患者的慢性高血糖会导致脂质过氧化产物在循环中积累，铁代谢途径受损，导致血浆中存在多种游离铁。铁死亡是一种新发现的细胞死亡形式，其特征是细胞内铁过载和铁依赖性脂质过氧化物的积累。这些表明铁死亡是糖尿病溃疡伤口愈合延迟的潜在机制之一，有望成为糖尿病患者伤口愈合延迟的新治疗靶点。本综述探讨了糖尿病溃疡伤口愈合的发病机制，揭示氧化应激和脂质过氧化是铁死亡和糖尿病溃疡伤口愈合延迟的共同病理机制。基于有力证据推测，铁死亡与糖尿病溃疡密切相关，具有深入研究的价值。我们试图从谷胱甘肽过氧化物酶4（GPX4）、铁过载、铁死亡抑制剂、晚期糖基化终产物（AGEs）和血红素加氧酶-1（HO-1）方面阐明铁死亡与糖尿病溃疡之间的潜在关联，为探索糖尿病溃疡的临床治疗提供新思路。
