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心脏特异性瘤亡因子-α的过度表达会导致小鼠腹膜氧化应激和收缩功能障碍
1Baylor College of Medicine and Texas Heart Institute, Houston, TX 77030, USA.
Circulation
|October 4, 2000
概括
患有心力衰竭的小鼠由于瘤缩因子-α (TNF-α) 的升高而表现出隔膜弱. 这种收缩功能障碍与增加的氧化压力有关,而不是组织重塑.
科学领域:
- 生理学 生理学 生理学
- 分子生物学分子生物学
- 心血管科学 心血管科学
背景情况:
- 转基因小鼠在心脏中过度表达瘤缩因子-α (TNF-α) 会发展为心力衰竭.
- 由于心脏溢出,人们观察到血液中的TNF-alpha水平升高.
- 已知TNF-alpha会导致呼吸道肌肉的缩和功能障碍.
研究的目的:
- 为了研究心脏受限TNF-α过度表达的转基因小鼠中的隔膜功能障碍.
- 为了确定隔膜的收缩损失是否是由氧化应激或组织重塑引起的.
主要方法:
- 在体外研究从转基因和对照小鼠的隔膜肌肉条.
- 直接电刺激以测量力量的产生.
- 使用光显微镜测量细胞质氧化剂水平.
- 评估N-乙半氨酸 (抗氧化剂) 和外源性TNF-alpha的作用.
主要成果:
- 与对照组相比,转基因小鼠的隔膜力产生显著减少 (47%).
- 在转基因小鼠的腹膜中观察到细胞内氧化剂水平的增加.
- 抗氧化剂治疗部分扭转了收缩性弱点.
- 外源性TNF-alpha在野生类型小鼠中诱导了类似的软弱和增加的氧化剂,N-乙半氨酸抑制了这种作用.
结论:
- 循环TNF-alpha的升高导致隔膜收缩功能障碍.
- 这种机制是一种由氧化应激介导的内分泌效应.
- 没有发现肌肉损伤或亡的证据,这表明TNF-alpha的影响是功能性的,而不是结构性的.
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