矿物皮类药物通过"非基因效应"加快过渡到心力衰竭,并通过"非基因效应"保持喷射分数
Selma F Mohammed1, Tomohito Ohtani, Josef Korinek
1Cardiovascular Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Circulation
|July 14, 2010
概括
高血压使心脏对矿物质皮质类药物过量敏感,加快心力衰竭与保存的射出分数. 这是通过氧化应激发生的,而不是经典的矿物质皮质醇受体通路.
科学领域:
- 心脏病学 心脏病学
- 生理学 生理学 生理学
- 分子生物学分子生物学
背景情况:
- 高血压心脏病进展到心力衰竭的机制与保存的喷射分数 (HFpEF) 仍然不清楚.
- 不管盐的状况如何,矿物质皮质类药物的过量都可能导致心脏缩,纤维化和心脏扩张功能障碍.
- 心脏的矿物质皮质体受体受到11-β基类固醇脱酶的保护,这表明炎症和氧化应激介导矿物质皮质体的影响.
研究的目的:
- 为了调查高血压心脏病是否与氧化压力有关.
- 为了确定高血压是否使心脏对矿物质皮质类药物过量敏感.
- 为了检查压力过载过重症中矿物质皮质类药物加速心脏重塑和功能障碍.
主要方法:
- 使用模拟操作和横向大动脉收缩 (TAC) 的小鼠模型在正常盐饮食中.
- 服用脱氧皮质乙酸盐 (DOCA) 来评估矿物质皮质过量.
- 测量了心脏结构,功能,氧化应激标志物 (骨质松丁,NOX4) 和矿物质皮质体受体基因转录.
主要成果:
- TAC小鼠表现出补偿高血压性心脏病与增高和增加氧化应激.
- 在TAC小鼠中,DOCA的使用加剧了缩,纤维化和腹功能障碍,导致HFpEF.
- 逐渐观察到氧化应激标记的增加,但经典的矿物质皮质类受体依赖基因转录并不明显.
结论:
- 压力过载缩使心脏对矿物质皮质类药物过量敏感.
- 在高血压心脏病的背景下,过多的矿物皮醇会加速过渡到HFpEF.
- 这种过渡似乎独立于经典的矿物质皮质体受体依赖基因转录,突出了氧化应激的作用.
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