坎塔里丁诱导的肠毒性:对肠壁破坏的分子洞察
Ruxia Liu1, Yuanyuan Xiao2, Qin Shen2
1School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China; The People's Hospital of Qianxi City, Qianxi, 551500, Guizhou, China.
Journal of ethnopharmacology
|August 24, 2025
概括
康塔里丁 (CTD) 通过破坏肠道屏障和微生物群的稳定性来损害小鼠的肠道. 这项研究揭示了CTD的肠毒性机制,涉及炎症途径和特定的基因表达.
科学领域:
- 药理学和毒理学
- 胃肠病学
- 微生物组研究
背景情况:
- 坎塔里丁 (CTD) 是一种传统的中药,用于治疗癌症,但其肠毒性不明.
- 了解CTD的肠道损伤机制对于其临床应用至关重要.
研究的目的:
- 研究CTD引起的小鼠肠道损伤.
- 探索CTD诱导肠道毒性的潜在机制.
主要方法:
- 组织学,西方抹杀和16S rRNA测序用于评估结肠损伤和肠道微生物群的变化.
- 综合转录组学和网络毒理学确定了CTD的分子机制.
- 分子对接和qPCR验证了潜在的治疗点.
主要成果:
- CTD降低了体重,结肠长度和小高度,降低了肠道屏障蛋白 (occludin,claudin-1,ZO-1).
- CTD改变了肠道微生物群,减少了有益的Akkermansia muciniphila,增加了像Helicobacter hepaticus这样的病原体.
- 转录组学发现687个不同表达的与炎症途径相关的基因,确定了6个核心目标.
结论:
- 在小鼠中,CTD会破坏肠道屏障和微生物群的平衡.
- 机制包括炎症基因 (Ifng,Cxcl9,Cxcl10,Ccl4,Il1a,Il1b) 和相关途径的上调.
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