白藜芦醇通过激活 NRF2/GPX4 通路抑制脊髓损伤小鼠的铁死亡,Microscopy Research and Technique

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白藜芦醇通过激活 NRF2/GPX4 通路抑制脊髓损伤小鼠的铁死亡
Microscopy Research and Technique ( IF 2.0 ) Pub Date : 2023-05-02 , DOI: 10.1002/jemt.24335
Chengtao Ni ₁ , Qing Ye ₂ , Xiaodan Mi _{2,

3} , Dian Jiao ₄ , Shuangshuang Zhang ₁ , Ruidong Cheng ₂ , Zhanglu Fang ₅ , Marong Fang ₆ , Xiangming Ye _{1,

2}

Affiliation

铁死亡是一种新定义的细胞死亡形式，与神经系统疾病有关。白藜芦醇是一种非黄酮类多酚化合物，具有抗炎和抗氧化特性，但其治疗脊髓损伤（SCI）的潜在治疗机制仍不清楚。因此，本研究评估白藜芦醇促进 SCI 小鼠神经和运动功能恢复的机制。使用巴索小鼠量表评分和足迹测试评估小鼠的运动功能。使用 NeuN、氟玉 C 和尼氏染色观察白藜芦醇对神经元细胞状态的影响。采用Perls蓝和二氨基联苯胺染色观察损伤节段铁含量的表达。还研究了白藜芦醇对丙二醛、谷胱甘肽、Fe ²⁺和谷胱甘肽过氧化物酶 4 酶活性水平的影响。透射电镜观察损伤节段细胞线粒体超微结构，Western blot检测铁死亡相关靶点蛋白水平。我们的研究结果表明，白藜芦醇可以改善 SCI 后的运动功能，并具有一定的神经保护作用；在铁死亡相关研究中，白藜芦醇抑制铁死亡相关蛋白质和离子的表达。白藜芦醇改善线粒体形态的变化。从机制上讲，Nrf2抑制剂ML385逆转了白藜芦醇对铁死亡相关基因的抑制作用，表明白藜芦醇通过Nrf2/GPX4途径抑制铁死亡。我们的研究结果阐明白藜芦醇促进功能恢复，抑制SCI后铁死亡，为后续临床转化研究提供实验基础。

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

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, Fe²⁺, 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 resveratrol inhibits ferroptosis through the Nrf2/GPX4 pathway. Our findings elucidate that resveratrol promotes functional recovery, inhibits ferroptosis post-SCI, and provides an experimental basis for subsequent clinical translational research.

更新日期：2023-05-02

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