高流动性组盒子-1 在心脏缺血-再输血损伤中的心脏
Martin Andrassy1, Hans C Volz, John C Igwe
1Department of Medicine III, University of Heidelberg, Heidelberg, Germany.
Circulation
|June 25, 2008
概括
高流动性组盒子-1 (HMGB1) 通过激活通过RAGE的炎症途径加剧心脏缺血/反 (I/R) 损伤. 阻断HMGB1,特别是HMGB1盒子A,显著减少心肌损伤,并可能提供一种新的治疗方法.
科学领域:
- 心脏病学 心脏病学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 高流动性组盒-1 (HMGB1) 是受压力细胞释放的核因子.
- HMGB1通过托尔类受体和先进糖化终产品 (RAGE) 的受体发出信号.
- 对于HMGB1在心脏缺血/再输血 (I/R) 损伤中的作用尚不清楚.
研究的目的:
- 调查HMGB1在心脏I/R损伤早期阶段的作用.
- 探索参与HMGB1介导的心脏损伤的信号通路.
- 评估HMGB1抑制在心脏I/R损伤中的治疗潜力.
主要方法:
- 在受到心脏I/R损伤的小鼠中评估HMGB1水平.
- 给小鼠使用重组HMGB1或HMGB1抗剂 (HMGB1盒子A).
- 利用RAGE缺陷 (RAGE-/-) 的小鼠来评估RAGE的参与.
- 在孤立的巨细胞中研究了炎症反应.
主要成果:
- 在心脏I/R损伤的早期,HMGB1水平升高.
- 重组HMGB1恶化了I/R损伤,而HMGB1盒子A减少了心脏病发作的大小.
- 抑制HMGB1涉及基激活蛋白激酶 (MAPKs) 和核因子-kappaB (NF-κB).
- 显著地保护RAGE缺陷免受I/R损伤和巨细胞中HMGB1诱导的炎症.
结论:
- HMGB1是心脏I/R损伤的关键早期调解者.
- 与RAGE结合的HMGB1激活了促炎途径,增强了心肌损伤.
- 准HMGB1为I/R损伤提供了一个有前途的治疗策略.
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