摘要
Diabetic nephropathy (DN), one of the most common and severe microvascular complications of diabetes, significantly increases the risk of renal failure and cardiovascular events. A high-glucose environment can lead to mitochondrial dysfunction in macrophages, which, through remodeling of energy metabolism, mediates the polarization of a pro-inflammatory phenotype and contributes to the formation of a chronic inflammatory microenvironment. Recent studies have found that high-glucose stimulation induces dysregulation of the nuclear factor erythroid 2-related factor 2 (NRF2) redox pathway in macrophages, leading to the generation of oxidative stress (OS) that further drives chronic inflammation. Therefore, it is crucial to fully understand how OS affects macrophage phenotypes and functions following NRF2 inhibition. This review analyzes the role of OS induced by NRF2 dysfunction in the chronic inflammation of DN and explores the relationship between OS and macrophage mitochondrial energy metabolism through the NAD⁺/NADH-SIRT3 axis, providing new therapeutic targets for targeting OS to improve the inflammatory microenvironment and vascular damage in DN.
摘要译文
糖尿病性肾病（DN）是糖尿病最常见和严重的微血管并发症之一，可显着增加肾衰竭和心血管事件的风险。高葡萄糖环境可导致巨噬细胞中的线粒体功能障碍，通过重塑能量代谢，介导了促炎性表型的极化，并有助于形成慢性炎症微环境。最近的研究发现，高葡萄糖刺激会诱导巨噬细胞中核因子2相关因子2（NRF2）氧化还原途径的失调，从而导致氧化应激（OS）产生，从而进一步驱动慢性炎症。因此，完全了解OS在NRF2抑制后如何影响OS如何影响巨噬细胞表型和功能至关重要。这篇综述分析了NRF2功能障碍诱导的OS在DN慢性炎症中诱导的作用，并通过NAD⁺/NADH-SIRT3 Axis探索OS与巨噬细胞线粒体能量代谢之间的关系，从而为靶向OS提供了新的治疗靶标，以靶向OS，以改善炎症性微环境损害和dn dn中的炎症性微观损害。
Runyuan Li; Xiaoyu Yan; Yuanxin Zhao; Huan Liu; Jian Wang; Yuan Yuan; Qianyuan Li; Jing Su. Oxidative Stress Induced by Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Dysfunction Aggravates Chronic Inflammation Through the NAD+/SIRT3 Axis and Promotes Renal Injury in Diabetes[J]. Antioxidants, 2025,14(3): 267