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治疗性S100A8/A9阻塞抑制心肌和全身炎症,并减轻败血症引起的心肌功能障碍
Gabriel Jakobsson1,2, Praveen Papareddy3, Henrik Andersson4
1Department of Translational Medicine, Lund University, Lund, Sweden.
Critical care (London, England)
|September 29, 2023
概括
阻断S100A8 / A9,一种促炎蛋白,有效地治疗小鼠的败血症诱导的心肌功能障碍. 这种方法表明,作为严重败血症患者心脏问题的新疗法策略有前途.
科学领域:
- 心脏病学 心脏病学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 败血症诱导的心肌功能障碍 (SIMD) 的触发因素不明,缺乏有效的治疗方法.
- S100A8/A9是一种在感染期间由中性粒细胞释放的促炎性警示剂.
- 调查S100A8/A9阻塞为SIMD提供了潜在的新治疗途径.
研究的目的:
- 评估血S100A8/A9水平与严重败血症患者心脏功能障碍之间的关系.
- 用ABR-238901评估S100A8/A9阻塞在内毒素引起的心脏功能障碍的小鼠模型中的有效性.
- 阐明S100A8/A9抑制在败血症期间对心肌功能的治疗和机制效应.
主要方法:
- 在62名严重败血症患者中评估了血S100A8/A9和心脏功能.
- 在野外型和S100A9淘汰赛小鼠中使用ABR-238901的S100A8/A9阻塞,这些小鼠遭受了LPS诱导的内毒性.
- 在不同时间点服用ABR-238901以评估心脏功能障碍的预防和逆转.
主要成果:
- 在败血症患者中,血S100A8/A9升高与左心室 (LV) 缩功能障碍和较高的SOFA得分相关.
- 在小鼠中,ABR-238901治疗预防并逆转了LPS诱导的LV功能障碍,表现优于德克萨米他.
- 抑制S100A8/A9降低了炎症媒介,炎症基因表达,并恢复了线粒体功能,S100A9淘汰赛小鼠显示出保护.
结论:
- 高S100A8/A9水平与严重败血症患者和小鼠模型中的LV功能障碍有关.
- 用ABR-238901的药理S100A8/A9阻塞显示出强大的抗炎作用,并减轻心肌功能障碍.
- 针对S100A8/A9代表了严重败血症患者的心脏并发症的有前途的新疗法策略.
关键词:
末端毒性病 (Endotoxemia) 是一种导致内毒性病的疾病.炎症 炎症是一种炎症.线粒体功能 线粒体功能中性粒细胞中性粒细胞.S100A8 / A9 / A9 / S100A8 / A9 / S100A8 / A9 / S100A8 / A9 / S100A9 / S100A8 / S100A9 / S100A9 / S100A8 / S100A9 / S100A9 / S100A9 / S100A8 / S100A9 / S100A9 / S100A9 / S100A8 / S100A9 / S100A9 / S100A8 / S100A9 / S100A9 / S100A8 / S100A9 / S100A9 / S100A8 / S100A9 / S100A8 / S100A9 / S100A9 / S100A8 / S100A9 / S100A8 / S100A9 / S100A8 / S100A9 / S100A8 / S100A9 / S100A8 / S100A8 / S100A9 / S100A8 / S100A9败血症引起的心肌功能障碍相关概念视频
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