托桑达宁通过通过抑制STAT3/CTSC轴来抑制自和溶酶体功能来诱导肝毒性
Li Luo1, Jiajie Ni1, Jiahui Zhang1
1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Toxicology letters
|March 9, 2024
概括
托桑达宁 (TSN) 通过阻断通过STAT3/CTSC通路的自细胞的发生导致肝损伤. 抑制STAT3会恶化TSN诱导的肝损伤和自抑制.
科学领域:
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
背景情况:
- 来自Melia toosendan的托森丹尼 (TSN) 显示出治疗潜力,但已知有肝毒性.
- 自失调与TSN诱导的肝损伤有关,但机制尚不清楚.
研究的目的:
- 研究信号传感器和转录3激活器 (STAT3) 在TSN诱导的自抑制和肝损伤中的作用.
- 阐明TSN肝毒性背后的分子机制.
主要方法:
- 利用Stat3淘汰赛C57BL/6小鼠和HepG2细胞来研究TSN影响.
- 评估了细胞活力,乳酸脱酶 (LDH),阿斯巴酸胺酶 (AST) 和氨酸转移酶 (ALT) 的水平.
- 分析了Janus激酶2 (JAK2) /STAT3通路,甲素C (CTSC) 表达和自标志物.
主要成果:
- 在体外和体内,TSN表现出显著的肝毒性,降低细胞活力和增加肝酶.
- TSN抑制了JAK2 / STAT3通路并减少了CTSC表达,导致自抑制.
- STAT3抑制加剧了TSN诱导的肝损伤和自阻塞,而STAT3激活减弱了这些影响.
- 发现STAT3通过转录调节CTSC,影响自和肝损伤.
结论:
- 通过抑制STAT3/CTSC轴依赖的自和溶酶体功能,TSN会导致肝毒性.
- 针对STAT3/CTSC通路提供了一种潜在的策略,以减轻TSN诱导的肝损伤.
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