瘤亡因子-α介于压力过载状态后的心脏重塑和心室功能障碍
Mei Sun1, Manyin Chen, Fayez Dawood
1The Heart and Stroke/Richard Lewar Centre of Excellence and Toronto General University Health Network, Toronto, Ontario, Canada.
Circulation
|March 14, 2007
概括
瘤亡因子-α (TNF-α) 驱动不良的心脏重塑和功能障碍后的压力过载. 在小鼠中抑制TNF-alpha可以减轻心脏缩,炎症和改善心脏功能.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 心脏病理生理学 心脏病理生理学
背景情况:
- 压力过重会诱导心肌细胞亡,增大和炎症,导致心力衰竭.
- 在压力过度后,瘤亡因子-α (TNF-α) 在心肌上升调节.
- 对于TNF-alpha在调节心脏对机械压力的反应中的确切作用尚未完全理解.
研究的目的:
- 调查TNF-alpha在调节心脏炎症反应,细胞外矩阵稳态和压力过载下的高的作用.
- 为了确定TNF-alpha是否有助于由机械过载引起的心室功能障碍.
主要方法:
- 使用C57/BL野生型和TNF-Knockout小鼠接受了下降大动脉带带或假手术.
- 评估了心脏TNF-alpha水平,肌细胞亡,高,炎症标志物,矩阵金属蛋白酶-9活性和心脏功能.
- 野生类型和TNF-knockout小鼠在主动脉带带后的结果比较.
主要成果:
- 大动脉带纹显著增加了心脏TNF-alpha,肌细胞亡,增大和炎症在野生类型的小鼠.
- 野生型小鼠在带带后表现出较高的矩阵金属蛋白酶-9活性和心脏功能受损.
- 脱离TNF的小鼠表现出减弱的心脏亡,增大,炎症和纤维化,心脏功能得到改善,MMP-9活性降低.
结论:
- 在压力过载期间,TNF-alpha在调解不利的左心室重塑中发挥着关键作用.
- 该研究表明,TNF-alpha调节心脏修复和重塑过程,有助于心室功能障碍.
- 准TNF-alpha可能为因压力过载而导致的心力衰竭提供治疗策略.
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