丁酸盐通过调节Nrf2/GPX4信号通路并改善肠道屏障,改善了性结肠炎中的铁亡
Hangping Chen1, Yifan Qian2, Chensheng Jiang3
1Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou 311200, Zhejiang, China.
Biochimica et biophysica acta. Molecular basis of disease
|December 7, 2023
概括
酸丁酸 (NaB) 通过抑制铁亡,一种涉及铁的细胞死亡途径,缓解性结肠炎 (UC). 这种治疗保护了肠道屏障,并减少了结肠炎模型中的炎症.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 性结肠炎 (UC) 涉及氧化应激和肠道炎症.
- 铁,标志着铁的积累和脂质过氧化,与UC病理有关.
- 在结肠炎模型中观察到减少的酸盐生产细菌和酸盐水平.
研究的目的:
- 研究甲酸盐 (NaB) 在治疗UC中的精确机制.
- 探索铁化在UC中的作用和NAB对这一过程的影响.
主要方法:
- 在小鼠模型中诱导大肠炎.
- 评估铁亡标志物 (炎症反应,铁含量,线粒体变化,蛋白质表达).
- 16S rRNA测序和GC-MS用于微生物群和短链脂肪酸分析.
- Nrf2敲击,以评估其在 NaB 的保护作用中的作用.
主要成果:
- 在大肠炎模型中证实了铁亡.
- NaB治疗显著改善了结肠炎症状,包括体重减轻和结肠缩短.
- NaB抑制了ferroptosis,改善了肠道屏障的完整性,并抑制了pro-ferroptosis蛋白质.
- NaB上调了抗铁灭的标志物Nrf2和GPX4;Nrf2倒置逆转了NaB的保护作用.
结论:
- 通过改善ferroptosis,NaB显示出对实验性结肠炎的保护作用.
- 该机制涉及Nrf2/GPX4信号通路和改善肠道屏障完整性.
- NaB为预防UC提供了一种新的治疗策略.
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