直接证据表明,瘤亡因子-α在动脉形成中的信号
Imo E Hoefer1, Niels van Royen, John E Rectenwald
1Department of Cardiology, University of Freiburg, Germany. hoefer@med1.ukl.uni-freiburg.de
Circulation
|April 10, 2002
概括
瘤亡因子-阿尔法 (TNF-α) 促进动脉形成,在动脉堵塞后恢复血液流动. 缺乏TNF-alpha或其p55受体的小鼠显著减少了附带动脉形成,突出显示了TNF-alpha.
科学领域:
- 心血管生物学 心血管生物学
- 炎症研究 炎症研究
- 血管生物学 血管生物学
背景情况:
- 动脉形成对于在动脉堵塞后恢复血液流动至关重要.
- 诸如瘤亡因子-α (TNF-α) 等炎症媒介在动脉生成中的作用尚未完全理解.
- 一个基于微球的新型小鼠模型被开发用于研究后肢 perfusion.
研究的目的:
- 研究TNF-alpha及其受体在动脉生成中的作用.
- 测试该假设,在没有功能性TNF-alpha或其p55受体的情况下,动脉生成受损.
主要方法:
- 在基因改造小鼠 (TNF-alpha-/-, p55-/- , p75-/-) 和对照中单侧股骨动脉的封闭.
- 使用激光多普勒和光微球测量后肢 perfusion.
- 在不同小鼠模型中对附带动脉 perfusion 恢复进行比较.
主要成果:
- 激光多普勒显示急性流量下降,但在1周后错误地正常化了值.
- 微球分析显示,对照小鼠在7天内恢复了~50%的 perfusion.
- 在TNF-α-/-小鼠中,附带输液减少了45.1%;在p55-/-小鼠中,附带输液减少了45.8% (P<0.01).
- p75-/-小鼠表现出与对照组相比的输液水平 (P=0.13).
结论:
- 微球技术对于剖析动脉生成机制非常有价值.
- TNF-α在调节动脉生成方面发挥着积极的作用.
- p55受体可能是TNF-alpha在动脉生成中的主要信号通路.
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