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HIF1A/BNIP3通路通过与BCL-2结合影响败血症诱导心肌病中的铁亡

Xiaoyue Wang¹, Jinze Li¹, Yixin Zhang²

¹The First Affiliated Hospital of Shihezi University, Shihezi, People's Republic of China.

Redox report : communications in free radical research

|August 8, 2025

概括

缺氧诱导因子-1α (HIF-1α) 和BNIP3通过促进铁死来加剧败血症诱导的心肌病. 抑制这种途径或BNIP3保护心脏,揭示新的治疗点.

科学领域:

心血管生物学心血管生物学
细胞死亡机制细胞死亡机制
分子信号传输的方法

背景情况:

败血症诱导心肌病 (SIC) 的特征是铁,一种依赖铁的细胞死亡途径.
缺氧诱导因子-1α (HIF-1α) 在SIC期间铁死中的作用尚未完全理解.
这项研究探讨了HIF1A/BNIP3途径与SLC7A11/GPX4铁亡轴在心肌损伤中的相互作用.

研究的目的:

调查HIF1A/BNIP3信号通路在败血症引起的心肌损伤期间铁亡中的作用.
为了阐明HIF1A/BNIP3和SLC7A11/GPX4铁灭轴之间的相互作用.
确定SIC的潜在治疗点.

主要方法:

已建立的小鼠模型使用结和穿孔 (CLP) 的败血性心肌损伤,以及使用LPS处理的H9c2细胞的体外模型.
给CLP大鼠使用HIF1A抑制剂 (LW6) 和铁灭抑制剂 (Fer-1).
在用LPS治疗的H9c2细胞中利用BNIP3敲除和芬班达 (FZ) 来评估细胞活力,ROS和蛋白质相互作用.

主要成果:

激活HIF1A/BNIP3信号会加剧败血性心肌损伤和铁亡,而抑制会改善这些影响.
在试验室中,BNIP3倒置显著降低了LPS诱导的心肌损伤和ferroptosis.
发现BNIP3和BECN1在BCL-2结合方面竞争,影响与铁亡相关的信号传递.

结论:

在SIC中,BCL-2起到HIF1A/BNIP3和BECN1/SLC7A11/GPX4通路之间的关键联系作用.
HIF1A/BNIP3通路在感染性心肌损伤中促进铁亡方面发挥着重要作用.
针对HIF1A/BNIP3-BCL-2-BECN1轴为SIC提供了一个有希望的治疗策略.

关键词:

在BCL-2中.在 BECN1/SLC7A11/GPX4 中.在 HIF-1α/BNIP3 中.败血症引起的心肌病变性.灭症 (apoptosis) 是一种死亡的过程.自自是自的过程.铁性化 (ferroptosis) 是一种心肌损伤是指心肌损伤.

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