氨基酸B4通过激活SRC介导的PI3K/AKT/mTOR通路来改善败血性心肌病,以缓解线粒体功能障碍和心肌细胞衰老
Yuan Fang1, Boshen Yang1, Dongfei Zhu2
1The Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
International immunopharmacology
|January 6, 2026
概括
化物B4 (AB4) 通过通过SRC介导的PI3K/AKT/mTOR途径增强心脏功能和线粒体健康,同时抑制细胞衰老,从而保护免受败血性心肌病 (SCM).
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 败血性心肌病 (SCM) 是败血症的严重并发症,其特征是心脏功能障碍.
- 线粒体功能障碍和心肌细胞衰老是SCM病变发生的关键因素.
- 对SCM有效的治疗策略仍然有限.
研究的目的:
- 为了研究Anemoside B4 (AB4) 对SCM的保护作用.
- 阐明底层机制,重点关注线粒体功能和细胞衰老.
- 探索SRC介导的PI3K/AKT/mTOR通路的作用.
主要方法:
- 已建立的LPS和CLP诱导的SCM小鼠模型和LPS刺激的H9c2心肌细胞.
- 给药剂量分级的AB4和使用SRC抑制剂PP2用于救援实验.
- 评估心脏功能,心肌损伤,蛋白质表达,基因表达和AB4-SRC结合.
主要成果:
- AB4证明了对SCM的剂量依赖性保护,改善心脏功能并减少心肌损伤.
- AB4直接与SRC结合,激活PI3K/AKT/mTOR通路,恢复了线粒体功能和形态.
- AB4抑制了心肌细胞衰老和与衰老相关的分泌表型 (SASP) 因素;SRC抑制否定了这些效应.
结论:
- AB4显示出作为SCM治疗剂的前景.
- AB4的保护作用由SRC-PI3K/AKT/mTOR途径调解,改善线粒体功能并抑制衰老.
- 准这种途径为治疗败血症引起的心脏损伤提供了潜在的策略.
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