甘西 (Gancao Xiexin) 开通过抑制ACSL4介导的铁灭症减轻了实验性结肠炎
Zengfeng Pan1, Caiyan Gan1, Shaobin Zhi2
1Institute of Basic Medical Sciences, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China; Guangdong Engineering Technological Research Center of Clinical Molecular Diagnosis and Antibody Drugs, Meizhou, China.
Journal of ethnopharmacology
|February 24, 2025
概括
甘西 (GCXXD) 开制剂通过减少ferroptosis,一种涉及ACSL4.4.的细胞死亡途径来治疗性结肠炎 (UC). 这种传统的中医药保护了肠道屏障,缓解了UC的症状.
科学领域:
- 胃肠病学和肝病学
- 药理学和毒理学 药理学和毒理学
- 细胞生物学 细胞生物学
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性肠病,其特点是肠壁功能障碍.
- 肠道上皮细胞的过度铁亡会加剧与UC相关的损伤和结肠透性.
- 长链乙基-CoA合成酶4 (ACSL4) 对于铁化至关重要,它介导了脂质过氧化物积累.
研究的目的:
- 为了阐明甘西辛 (GCXXD) 的药理机制,用于治疗性结肠炎 (UC).
- 研究ACSL4介导的铁死在GCXXD对UC的治疗作用中的作用.
- 为了证明GCXXD通过调节ACSL4诱导的铁死来保护肠粘膜屏障.
主要方法:
- 分析GSE134025数据集和DSS诱导的实验性结肠炎模型.
- 使用罗西格利塔对ACSL4抑制的评估以及对UC小鼠进行GCXXD治疗 (9,12,15g/kg) 的评估.
- 转录组分析 (KEGG) 和同时使用ACSL4上游激动剂 (Py-60) 与GCXXD.
主要成果:
- 在UC患者中,ACSL4表达升高;其抑制和GCXXD治疗减少了UC症状.
- GCXXD改善了结肠长度,体重,粘素,奥克卢丁和克劳丁-1表达,同时降低了炎症.
- 确定了GCXXD下调的铁灭标志物 (MDA,Fe2+,COX2,ACSL4) 和上调的GPX4;TEAD4/ACSL4通路调节.
结论:
- 甘 (Gancao Xiexin) (GCXXD) 减轻了性结肠炎 (UC) 中的铁.
- 在UC中GCXXD的治疗效果可能通过TEAD4/ACSL4通路进行介导.
- 通过向ferroptosis和保持肠道屏障完整性,GCXXD显示出作为治疗UC的潜力.
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