在TERT缺乏的进发症小鼠中,线粒体氧化应激和心脏功能障碍
Zandong Zhou1, Yunpeng Zhang1, Rui Zhao2,3,4,5
1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin, China.
Clinical and experimental pharmacology & physiology
|October 14, 2025
概括
线粒体功能障碍和氧化应激驱动心脏衰老和心脏衰竭在小鼠与端粒缺乏. 准线粒体质量控制可能为与年龄有关的心力衰竭提供新的治疗方法.
科学领域:
- 心脏病学 心脏病学
- 老年学是一门学科.
- 线粒体生物学 线粒体生物学
背景情况:
- 心力衰竭是老年人住院的重要原因,患病率随年龄和高血压和糖尿病等危险因素而增加.
- 与衰老相关的心肌纤维化会损害心脏功能,但将线粒体氧化应激与衰老中的心脏重塑联系起来的机制尚不清楚.
研究的目的:
- 研究与衰老相关的腹腔电气和结构改造的机制.
- 确定线粒体功能障碍在与衰老相关的心力衰竭中的作用.
主要方法:
- 开发了第三代端粒酶逆转录酶缺乏 (TERT-/-) 孕症小鼠以模拟加速衰老.
- 使用心声学,组织学,心电学,心表图绘制,RNA测序和生物化学分析来评估心脏功能和重塑.
主要成果:
- TERT-/-小鼠表现出加速衰老,p53增加,间歇性纤维化和炎症,表明结构重塑.
- 显著的缩和扩张功能障碍,延长的QRS持续时间和减缓的心室导电速度表明了电气重塑.
- 线粒体氧化应激通路被上调,线粒体超结构被破坏,蛋白质表达被改变,突出了线粒体功能障碍的作用.
结论:
- 在TERT-/-小鼠中加速衰老导致显著的心脏损伤,包括由线粒体功能障碍和氧化应激驱动的电气和结构重塑.
- 线粒体氧化应激与与衰老有关的心力衰竭有关.
- 针对线粒体质量控制,为与衰老相关的心力衰竭提供了潜在的治疗策略.
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