在体内通过氧化快速调节血小板激活
Andreas Schäfer1, Frank Wiesmann, Stefan Neubauer
1Department of Cardiovascular Medicine, University of Oxford, UK.
Circulation
|April 7, 2004
概括
缺氧化 (NO) 迅速激活人类的血小板,增加心血管疾病的风险. 补充外源NO使血小板功能正常化,突出了NO的作用.
科学领域:
- 心血管生理学心血管生理学
- 血液静止和血栓形成
背景情况:
- 血小板激活是与内皮功能障碍有关的心血管疾病的标志.
- 氧化 (NO) 生物可用性与体内血小板激活之间的确切关系尚未完全理解.
研究的目的:
- 为了研究急性NO合成抑制对人类血小板激活的影响.
- 为了确定外源NO是否可以逆转NO抑制诱导的血小板激活.
主要方法:
- 健康的志愿者接受了N(G) -单甲基-l-氨酸以抑制NO合成酶,并监测血压和血小板VASP酸化.
- 通过测量纤维素原结合和P-选择素,糖蛋白53和CD40连接体的表达来评估血小板激活.
- 用NO的供体甘三酸盐来评估其对血小板功能的影响.
主要成果:
- 抑制NO合成酶导致血压升高和血小板VASP酸化减少,证实了NO途径的抑制.
- 血小板激活标志物,包括纤维蛋白结合和P-选择因表达,在NO合成酶抑制后显著增加.
- 舌下用甘三酸盐给药使血小板VASP酸化正常化,并将血小板激活标志物逆转至基线水平.
结论:
- 在人类中,急性内源性NO生产抑制迅速触发了活体中血小板激活.
- 外源NO的使用有效地逆转了NO抑制诱导的血小板激活.
- 活体中血小板功能可以通过氧化的生物可用性显而易见地快速调节.
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