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Updated: Jan 11, 2026

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A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
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心肌细胞GSDME通过准CCL2-CCR2轴驱动多克索鲁比诱导的心脏毒性
Junqiang Xue1, Shiyao Xie1,2, Xuelin Cheng3
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China.
International journal of biological sciences
|November 10, 2025
概括
加斯德明E (GSDME) 通过破坏心脏细胞并引发炎症,加剧了多克索鲁比诱导的心脏毒性. 向心肌细胞中的GSDME提供了一个有希望的策略来预防和治疗这种化疗副作用.
科学领域:
- 心脏病学 心脏病学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 多克索鲁比 (DOX) 化疗受心脏毒性限制.
- 加斯德明E (GSDME) 与心血管疾病有关,但其在DOX诱导心脏毒性 (DIC) 中的作用尚不清楚.
研究的目的:
- 调查GSDME在DIC发展中的作用.
- 确定GSDME作为管理DIC的潜在治疗目标.
主要方法:
- 检查了DOX处理的小鼠心脏和心肌细胞中的GSDME表达.
- 使用心肌细胞特异性GSDME淘汰小鼠.
- 评估心脏重塑,功能和纤维化.
- 分析了CCL2-CCR2信号和STING/NFκB通路的激活.
主要成果:
- 在DOX处理的心脏和心肌细胞中,GSDME的调节升高.
- 特定于心肌细胞的GSDME绝杀减弱了DOX诱导的心脏损伤和纤维化.
- 通过CCL2-CCR2轴,GSDME绝杀降低了心脏炎症.
- GSDME促进了线粒体损伤,并激活了STING/NFκB通路.
结论:
- 在DIC的发展中,GSDME发挥着至关重要的作用.
- 准心肌细胞中的GSDME是预防和治疗DIC的可行策略.
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