基于AMPK信号通路的基础上,氧α-sanshool对肝脏和肝细胞中的脂质代谢的影响
Qiwen Xiang1, Jiayu Wen1, Zhihui Zhou1
1School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
概括
氧-α-sanshool (HAS) 来自Zanthoxylum armatum DC. 这种化学物质的含量是多少? 通过破坏脂质代谢和线粒体功能,导致肝损伤. 这项研究揭示了HAS的肝毒性,影响了安全使用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 生物化学 生物化学
背景情况:
- 桑托克西亚马图姆 DC. (ZADC) 已因其药用而闻名,但表现出肝毒性.
- 特定的有毒化合物和ZADC诱导的肝损伤的机制仍然不清楚.
- 氧-α-sanshool (HAS),一种来自ZADC水果的胺,是一种潜在的肝毒素,但其作用尚未明确.
研究的目的:
- 为了研究HAS对肝脂代谢的影响.
- 阐明HAS导致肝脂积累的机制.
- 提供有关HAS管理的安全信息.
主要方法:
- 在体内研究中,对C57 BL/6 J小鼠施加了不同的HAS剂量,随后进行了生物化学和组织学分析.
- 在体外研究中,使用HAS治疗的HepG2细胞来评估细胞内脂质含量和线粒体功能.
- 参与脂质生成和代谢的关键蛋白质被分析使用西式涂抹,并评估线粒体功能 (膜潜力,ATP水平,呼吸链复合体).
主要成果:
- 在小鼠中,HAS的使用导致肝酶 (ALT,AST) 升高,肝指数增加和肝细胞亡.
- 血清和肝脏甘油三,总胆固醇和LDL-C显著增加,HDL-C下降.
- HAS治疗诱导了HepG2细胞中的脂质积累,减少了线粒体功能 (膜潜力,ATP,呼吸链活性),并通过抑制AMPK通路改变了调节脂质代谢的蛋白质的表达 (增加ACC,FASN,SREBP-1c;减少PPARα,CPT1).
结论:
- 氧α-sanshool (HAS) 具有显著的肝毒性作用.
- HAS通过促进脂肪酸合成和损害线粒体功能来诱导肝脏脂质的积累.
- 抑制AMPK信号通路是导致HAS诱导的肝损伤和异常脂质代谢的关键机制.
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