Abstract
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.