马特林通过Nrf2抗氧化系统在H9c2细胞中促进铁亡,诱导心脏毒性
Xi Wang1, Zixiong Lin1, Xinyi Tang1
1School of Medicine, Yichun University, 576 XueFu Road, Yuanzhou District, Yichun 336000, PR China.
Toxicology letters
|May 9, 2024
概括
马特林 (MT) 通过诱导氧化应激和Nrf2抗氧化系统失衡相关的过程铁亡,导致心脏细胞死亡. 针对铁亡的治疗或增强抗氧化防御的治疗可以减轻MT诱导的心脏毒性.
科学领域:
- 心脏病学 心脏病学
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 马特林 (MT) 显示出抗癌和抗肝炎作用,但具有剂量限制性毒性.
- 以前的研究发现了MT诱导的肝毒性和毒性.
- 的心脏毒性潜力在很大程度上仍未被探索.
研究的目的:
- 为了研究Matrine (MT) 在H9c2细胞中的心脏毒性.
- 阐明MT诱导的心脏损伤的潜在机制.
- 探索针对MT心脏毒性的潜在治疗干预措施.
主要方法:
- MT对H9c2细胞的处理.
- 评估细胞活力,膜完整性和氧化应激标志物 (GSH,Cys,Fe2+,脂质过氧化,ROS,MDA).
- 研究铁灭菌路径 (Fer-1,RSL3) 和关键蛋白质水平 (FTH,Nrf2,xCT,GPX4,FSP1,TFR1) 的研究.
- 对Nrf2转录活性和Nrf2激动剂 (DMF), (SS) 和CoQ10的保护作用的评估.
主要成果:
- MT诱导了显著的H9c2细胞死亡和膜损伤.
- 通过降低GSH/Cys和增加Fe2+,脂质过氧化,ROS和MDA,MT触发了铁.
- MT降低了铁灭调节蛋白 (FTH,Nrf2,xCT,GPX4,FSP1) 和Nrf2活性水平,同时增加了TFR1.
- 铁酶抑制剂/激动剂调节了MT效应;DMF,SS和CoQ10减轻了MT诱导的细胞毒性.
结论:
- 马特林 (MT) 在H9c2细胞中诱导心脏毒性,主要是通过铁亡.
- Nrf2抗氧化系统的失衡有助于MT诱导的铁亡和心脏损伤.
- 向铁或增强Nrf2介导的抗氧化防御可能提供针对MT心脏毒性的保护策略.
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