NETs通过NF-κB/ferroptosis轴驱动高血压中的心肌纤维化
Qingxian Tu1,2, Xiaowei Gong2, Xiaoxi Yuan2
1Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Frontiers in immunology
|January 29, 2026
概括
中性细胞细胞外陷 (NETs) 通过激活NF-κB和铁亡,导致心脏纤维化,加剧高血压心脏病 (HHD). 针对这些途径可能为HHD提供新的治疗方法.
科学领域:
- 心血管研究研究心血管研究
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 高血压心脏病 (HHD) 涉及慢性压力过载,导致心肌重塑和纤维化.
- 中性粒细胞外细胞陷 (NETs) 在与HHD相关的纤维化中的作用尚未完全理解.
- 炎症和细胞死亡途径是已知的纤维化贡献者.
研究的目的:
- 研究NETs在自发高血压大鼠 (SHRs) 心肌纤维化恶化的作用.
- 为了确定NET是否激活核因子-κB (NF-κB) 信号通路和ferroptosis在HHD的背景下.
- 阐明在高血压心脏纤维化中连接NETs,NF-κB和ferroptosis的分子机制.
主要方法:
- 使用自发高血压大鼠 (SHRs) 和Wistar-Kyoto (WKY) 大鼠进行比较分析.
- 评估心脏功能和纤维化,使用心声回声学,组织学和西式涂抹.
- 采用转录基因分析,免疫光学,ELISA,qPCR和细胞培养实验 (H9c2心肌细胞) 与特定抑制剂 (DNase I,Ferrostatin-1,JSH-23) 分析分子通路.
主要成果:
- SHRs显示血压升高,心脏功能受损,心肌纤维化显著与增加的原沉积.
- 转录基因和蛋白质基因分析揭示了上调的NET和铁亡标志物,以及SHR中激活的NF-κB信号.
- 实验室研究表明,NETs诱导铁亡并激活心肌细胞中的NF-κB,促进益菌性基因表达. 抑制NETs,ferroptosis或NF-κB可以减轻这些影响.
结论:
- 确定了一种涉及NETs,NF-κB和驱动高血压心肌纤维化的铁亡的病原性轴.
- NETs通过促进氧化应激和心肌细胞中依赖铁的细胞死亡来促进心脏纤维化.
- 针对NET形成或下游NF-κB和铁亡途径的治疗策略显示出对治疗HHD和保持心脏功能有希望.
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