Resveratrol inhibits ferroptosis via activating NRF2 / GPX4 pathway in mice with spinal cord injury

作者：Chengtao Ni, Qing Ye, Xiaodan Mi, Dian Jiao, Shuangshuang Zhang, Ruidong Cheng, Zhanglu Fang, Marong Fang, Xiangming Ye · 发表于：Microscopy Research and Technique · 年份：2023 · DOI：10.1002/jemt.24335 · 被引用次数：54 · 研究领域：Circular RNAs in diseases、Cancer-related molecular mechanisms research、Peroxisome Proliferator-Activated Receptors

Abstract Ferroptosis is a newly defined form of cell death involved in neurologic disease. Resveratrol is a non‐flavonoid polyphenolic compound with anti‐inflammatory and antioxidant properties, but its potential therapeutic mechanism in spinal cord injury (SCI) remains unknown. Therefore, this study evaluates the mechanism by which resveratrol promotes neurological and motor function recovery in mice with SCI. The motor function of mice was evaluated using the Basso Mouse Scale score and footprint test. The effect of resveratrol on the neuronal cell state was observed using NeuN, fluoro‐Jade C, and Nissl staining. The expression of iron content in injured segments was observed using Perls blue and Diaminobenzidine staining. The effect of resveratrol on the levels of malondialdehyde, glutathione, Fe 2+ , and glutathione peroxidase 4 enzyme activity was also investigated. The mitochondrial ultrastructures of injured segment cells were observed using transmission electron microscope, while the protein levels of ferroptosis‐related targets were detected using Western blot. Our findings show that resveratrol improves motor function after SCI and has certain neuroprotective effects; in ferroptosis‐related studies, resveratrol inhibited the expression of ferroptosis‐related proteins and ions. Resveratrol improved changes in mitochondrial morphology. Mechanistically, the Nrf2 inhibitor ML385 reversed the inhibitory effect of resveratrol on ferroptosis‐related genes, indicating that ...