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Murine Model of Hindlimb Ischemia
Published on: January 21, 2009
p66ShcA调节组织对后肢缺血的反应
Germana Zaccagnini1, Fabio Martelli, Pasquale Fasanaro
1Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.
Circulation
|June 3, 2004
概括
缺少p66ShcA蛋白质的小鼠在缺血和再注射后减少了组织损伤和细胞死亡. 这表明p66ShcA是这些损伤途径的关键,提供了潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生理学 生理学 生理学
背景情况:
- 氧化应激是缺血和缺血/反 (I/R) 损伤的核心.
- p66ShcA-null小鼠表现出减少的活性氧物种和增强的抗氧化应激诱导的细胞死亡的抵抗力.
研究的目的:
- 研究p66ShcA在急性缺血和I/R后组织损伤中的作用.
- 为了确定p66ShcA缺乏是否会改变对缺血性损伤的敏感性.
主要方法:
- 在p66ShcA野生型和p66ShcA-null小鼠中诱导单边后肢缺血和I/R.
- 评估血液输液,组织损伤 (毛细血管密度,肌肉纤维亡) 和亡水平.
- 在模拟的缺血条件下对分离细胞进行体外分析.
主要成果:
- 与野生类型相比,p66ShcA-null小鼠的毛细血管密度下降和肌肉纤维衰老明显较小.
- 在p66ShcA-null小鼠中观察到较低水平的亡性内皮细胞和肌纤维.
- 来自p66ShcA-null小鼠的细胞在试验室中表现出对亡的抵抗力,并减少了氧化应激.
结论:
- 在急性缺血和I/R激活的细胞死亡途径中,p66ShcA具有关键作用.
- 向p66ShcA为缓解缺血组织损伤提供了一个潜在的治疗策略.
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