皮层Dictamni诱导的肝毒性通过增强的氧化酸化:从整合性转录组学,蛋白质组学和代谢组学分析的见解
Huijuan Sun1, Yu Wang2, Geyu Deng1
1Graduate School, Heilongjiang University of Chinese Medicine, Harbin, PR China.
概括
皮层Dictamni (CD) 可以导致肝损伤,主要是通过影响NADH脱酶 (乌比金) Fe-S蛋白2 (Ndufs2) 和氧化酸化 (OXPHOS). 这项研究揭示了CD诱导的肝毒性背后的关键机制.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 传统中国医药 传统中国医药
- 肝病学 肝病学是一种肝病学.
背景情况:
- 皮层字体 (Cortex Dictamni,简称CD) 是一种传统的中医药,用于治疗皮肤疾病.
- 临床报告表明CD可以导致严重的肝毒性,但机制尚不清楚.
研究的目的:
- 为了阐明CD诱导的肝毒性的内在机制.
- 为了确定参与CD毒性的关键分子通路.
主要方法:
- 在SD大鼠和体外使用人类原发性肝细胞 (HPHs) 和分化HepaRG (dHepaRG) 细胞评估肝毒性.
- 使用超高性能液态色谱 (UPLC) 来确定CD组件.
- 采用集成的多组学 (转录组学,蛋白组学,代谢组学) 和机械验证 in vivo 和 in vitro.
主要成果:
- 在大鼠中,使用CD诱导了剂量依赖性肝毒性,肝酶和白蛋白水平发生变化.
- 综合多组学确定了NADH脱酶 (ubiquinone) Fe-S蛋白2 (Ndufs2) 作为通过氧化酸化 (OXPHOS) 诱导CD肝毒性的关键调节器.
- CD抑制了细胞活力,上调了Ndufs2,反应性氧物种 (ROS) 和线粒体呼吸链复合物I,导致了细胞亡和线粒体功能障碍.
结论:
- 这项研究提供了对CD毒性的全面了解,包括剂量依赖性.
- 在CD引起的肝毒性中,Ndufs2调节的OXPHOS的中心作用首次被确定.
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