含gp91phox的NADPH氧化酶在血管高血压中调解内皮功能障碍
O Jung1, J G Schreiber, H Geiger
1Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.
Circulation
|March 24, 2004
概括
内皮gp91phox NADPH氧化酶产生超氧化物,减少氧化的可用性,并在血管高血压中引起内皮功能障碍. 敲除gp91phox可以防止这种功能障碍.
科学领域:
- 血管生物学 血管生物学
- 高血压研究 高血压研究
- 氧化压力是一种氧化压力.
背景情况:
- NADPH氧化酶异型有助于血管超氧化 (*O2-) 的形成,影响氧化 (NO) 的生物可用性.
- 带有内皮gp91phox的NADPH氧化酶被假设为*O2的主要来源 - 清除内皮NO,导致内皮功能障碍.
研究的目的:
- 在血管高血压模型中研究内皮质gp91phox含NADPH氧化酶在内皮质功能障碍的发展中的作用.
- 确定抑制这种特定的NADPH氧化酶异型能否恢复内皮功能.
主要方法:
- 研究了来自野生型 (WT) 和gp91phox-knockout (gp91phox-/-) 小鼠的大动脉环,这些小鼠接受了动脉剪切 (2K1C) 来诱导血管高血压.
- 评估了依赖内皮的放松到乙胆 (ACh) 和放松到外源NO的放松.
- 使用了活性氧物种 (ROS) 清除剂和NADPH氧化酶抑制剂.
主要成果:
- 高血压在WT中比gp91phox-/-小鼠更严重.
- 在剪切的WT小鼠中,内皮依赖放松受损,但在剪切的gp91phox-/-小鼠中保持.
- ROS清理剂和NADPH氧化酶抑制剂在剪切的WT小鼠中改善了放松,而在gp91phox-/-小鼠中没有影响. 在剪切的WT小鼠中,对外源NO的放松被减弱.
结论:
- 内皮gp91phox含NADPH氧化酶衍生的*O2-形成是2K1C模型中NO生物可用性降低的原因.
- 这一途径显著促进血管高血压的发展和相关的内皮功能障碍.
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