在小鼠中,由内毒素诱导的心肌病和系统性炎症通过抑制阿尔多减少酶来预防
Kota V Ramana1, Monte S Willis, Michael D White
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Circulation
|October 13, 2006
概括
抑制阿尔多减少酶可以减少炎症和心血管功能障碍在败血症. 这种酶在败血症诱导的细胞因子生成和心脏损伤中发挥着关键作用,提供了潜在的治疗标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 心血管生理学心血管生理学
背景情况:
- 败血症涉及过度的炎症性细胞因子产生和心血管崩.
- 反氧化变化和脂质过氧化产物在败血症期间影响炎症信号.
研究的目的:
- 调查阿尔多缩酶在败血症引起的炎症和心血管功能障碍中的作用.
- 测试假设,阿尔多减少酶活性是炎症信号和细胞因子生成在败血症期间至关重要的.
主要方法:
- 药理上抑制阿尔多减少酶使用索尔比尼尔.
- 使用小干扰RNA对阿尔多减少酶进行 Knockdown.
- 在细胞和动物毒症模型中评估炎症标记物,信号通路激活和心脏功能.
主要成果:
- 抑制阿尔多缩酶可以防止激发细胞中的核因子-kappaB的激活和瘤坏死因子-alpha的释放.
- 抑制抑制了血清和心脏细胞因子的增加,以应对脂多糖.
- 索尔比尼尔治疗改善了心肌的分数缩短和保持心脏收缩功能,增加了致命性败血症小鼠模型中的存活率.
结论:
- 阿尔多斯减少酶可以调解内毒素诱导的炎症和心肌病.
- 抑制阿尔多缩酶可能是一种可行的策略,用于治疗败血症相关的心血管功能障碍和不适应宿主反应.
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