通过抑制氧化应激诱导的细胞亡,阻断内化细菌劫持细胞反应
Ruoyi Lv1, Ziwen Cai2, Zhigang Sun3
1Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, No.7 Beinong Road, Changping, Beijing 102206, China; Beijing Traditional Chinese Veterinary Engineering Center, Beijing University of Agriculture, No.7 Beinong Road, Changping, Beijing 102206, China.
International journal of antimicrobial agents
|August 22, 2025
概括
作为对抗持续性细菌感染的宿主导疗法, 这些化合物减少了细胞内细菌的定居,并通过抑制细胞亡来减轻宿主细胞的损伤.
科学领域:
- 微生物学
- 细胞生物学
- 药理学
背景情况:
- 内部细菌会通过劫持宿主细胞反应引起持续性感染.
- 传统的抗生素通常对细胞内细菌无效.
- 宿主导疗法正在成为一个有前途的替代方案, 但分子点尚不清楚.
研究的目的:
- 调查三种类型的抗菌素的宿主指导性活性:米瑞,卡姆菲罗尔和奎尔塞.
- 鉴定细胞内细菌感染的黄中介抑制的分子机制和点.
- 评估黄作为治疗细菌引起的持久性感染的潜力.
主要方法:
- 用弗拉沃治疗肺上皮细胞以对抗内化黄金菌和肺炎菌.
- 细胞内细菌殖民和抗生素敏感性的定量分析 (MBCIN与MBcex).
- 应用网络药理学和转录组学来识别分子标.
- 反应性氧物种 (ROS) 生产和线粒体膜潜能 (ΔΨm) 的评估.
- 在体外和体内研究细胞死亡途径,包括PI3K/Bcl-2和caspase-9/caspase-3级联.
主要成果:
- 黄治疗显著降低了细胞内细菌的殖民化 (大约 降低了细胞内最小杀菌度 (MBCIN) 与细胞外最小杀菌度 (MBCex) 相比.
- 网络药理学和转录组学发现抑制细胞死亡是关键机制.
- 黄醇降低了ROS的产生并恢复了线粒体膜潜能 (ΔΨm),从而减轻了细菌内化诱导的亡.
- 具有最高酸含量的myricetin显示出最显著的效果.
- 调节PI3K/Bcl-2和caspase-9/caspase-3信号通路以缓解细胞灭绝.
结论:
- 梅西丁,卡姆菲罗尔和奎尔塞丁对内化细菌具有显著的宿主导抗菌特性.
- 通过调节ROS,线粒体功能和特定信号级联来保护宿主上皮细胞免受细菌诱导的亡.
- 这些发现强调了黄在对抗由细胞内病原体介导的持续性感染方面的治疗潜力.
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