在用抗结核药物治疗后,HepG2细胞的分子和细胞重塑
Shikha Bakshi1, Maninder Kaur1, Arpana Verma1
1Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Journal of biochemical and molecular toxicology
|May 31, 2023
概括
结核病治疗产生的药物诱导的肝损伤会伤害患者. 这项研究揭示了抗结核药物如何通过增加氧化应激,改变线粒体,减少自,影响细胞存活来损害肝细胞.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 药物诱导性肝损伤 (DILI) 是结核病治疗的一个显著不良影响.
- DILI使治疗复杂化,导致不服药和耐药性.
- 从一线抗结核药物 (ATD) 产生DILI的机制需要进一步阐明.
研究的目的:
- 为了研究ATD引起的DILI的细胞机制.
- 了解ATD毒性如何影响肝细胞生存策略.
- 为了识别高ATD度诱导的细胞损伤途径.
主要方法:
- 利用HepG2细胞作为肝细胞的体外模型.
- 评估ATD治疗后的细胞形态变化 (穿孔,形状,斑点).
- 使用MitoRed追踪器测量了线粒体膜的透性.
- 量化反应性氧物种 (ROS) 生产和谷氨水平.
- 通过基因表达评估了亡和自标志物 (Atg5,Atg7,LC3B).
主要成果:
- 高度的ATD诱导HepG2细胞显著的形态变化.
- ATD毒性导致线粒体膜的透性增加和ROS的产生.
- 谷氨水平下降,而亡标志物在高ATD剂量下增加.
- 关键的自标志物 (Atg5,Atg7,LC3B) 的表达显著降低.
结论:
- 由ATD引起的毒性会损害肝细胞处理细胞损伤的能力.
- 机制包括改变的线粒体功能,升高的亡和抑制的自.
- 这些发现突显出需要辅助疗法来减轻ATD肝毒性.
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