乌尔索多西胆酸可以缓解大动脉动脉瘤和通过肠道的Farnesoid X受体/胺合成酶2轴的剖析
Zhaofeng Zhang1,2,3, Linfeng Xie1,2,3, Xinfan Lin1,2,3
1Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Communications biology
|July 5, 2025
概括
乌尔索多西胆酸 (UDCA) 可能为大动脉动脉瘤和解剖 (AAD) 提供一种新的治疗方法. UDCA抑制了肠道的Farnesoid X受体 (FXR) 激活,减少了疾病发生率和细胞外基质降解.
科学领域:
- 心血管研究研究心血管研究
- 胃肠病学 胃肠病学
- 代谢疾病 代谢疾病
背景情况:
- 大动脉动脉瘤和剖析 (AAD) 是严重的心血管疾病,治疗选择有限.
- 已知 Ursodeoxycholic 酸 (UDCA) 可以延迟代谢疾病,如2型糖尿病和肥胖症.
- 目前尚不清楚UDCA在预防AAD方面的潜力.
研究的目的:
- 为了研究肠道法尔内索伊德X受体 (FXR) 在ADD病变发生中的作用.
- 为了确定UDCA是否可以通过向肠道FXR来预防AAD.
- 阐明将肠道FXR与AAD联系起来的分子机制.
主要方法:
- 在AAD患者和小鼠中对肠道FXR激活的病理分析.
- 在体内实验中使用腺相关病毒 (AAV) 进行小鼠肠道FXR敲击.
- 实验室研究评估肠道FXR激活对胺合成和细胞外基质降解的影响.
主要成果:
- 在AAD患者和小鼠中观察到肠道FXR的病理激活.
- UDCA治疗显著抑制了肠道的FXR激活.
- 肠道FXR敲击降低了AAD发生率,巨细胞透和细胞外基质降解.
- 肠道FXR激活增加了胺合成酶2 (Cers2) 的表达,导致C20胺释放.
- C20胺促进了细胞外矩阵金属蛋白酶 (MMP) 的释放,有助于AAD.
结论:
- 肠道FXR在AAD的发展中起着至关重要的作用.
- 通过抑制肠道FXR,UDCA显示出对AAD的治疗潜力.
- 肠道的FXR/Cers2轴代表了AAD的一种新的治疗点.
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