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Nrf2激活可以改善实验性类风湿性关节炎
Anqi Zhang1, Takafumi Suzuki1, Saki Adachi2
1Departments of Biochemistry and Molecular Biology, Tohoku Medical-Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Departments of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
Free radical biology & medicine
|July 26, 2023
概括
激活Nrf2 (核素红色素2相关因子2) 有效地治疗小鼠类风湿性关节炎. 这种方法可以减少炎症并增强抗氧化防御,为这种疾病提供了一个有前途的新治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 自免疫性疾病 自免疫性疾病
- 分子生物学分子生物学
背景情况:
- 类风湿性关节炎是一种全身性自身免疫性疾病,导致关节疼痛和功能障碍.
- 目前用于类风湿性关节炎的治疗方法存在严重不良影响的风险.
- 需要新的治疗策略,以提高安全性.
研究的目的:
- 在类风湿性关节炎小鼠模型中研究核红素因子2相关因子2 (Nrf2) 激活的治疗潜力.
- 确定Nrf2激活影响关节炎炎炎症和氧化应激途径的机制.
主要方法:
- 使用SKG小鼠,在注射齐莫桑A后发展T细胞介导的自身免疫性关节炎.
- 使用基因Nrf2激活通过Kelch-like ECH相关蛋白1 (Keap1) 敲击.
- 服用CDDO-Im,一种化学Nrf2诱导剂,以评估其预防和治疗效果.
- 在孤立的纤维细胞样同胞细胞 (FLS) 中分析了促炎性细胞因子和抗氧化酶的基因表达.
主要成果:
- 在SKG小鼠中,基因Nrf2通过Keap1敲击激活显著抑制了关节炎.
- Nrf2激活抑制了促炎性细胞因子表达,并诱导了抗氧化酶表达.
- 口服CDDO-Im以Nrf2-依赖的方式显示出对关节炎的预防和治疗作用.
- 在纤维细胞样同胞细胞中Nrf2的激活导致了益炎性细胞因子的减少和抗氧化酶基因表达的增加.
结论:
- 在SKG实验性类风湿性关节炎模型中,Nrf2激活具有显著的抗关节炎作用.
- 向Nrf2代表了对类风湿性关节炎的有前途的新疗法策略.
- 这些发现突出了Nrf2在调节关节炎症和氧化途径方面的作用,这与类风湿性关节炎的发病相关.
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