瘤坏死因子受体1在缺血期间在女性心肌中信号抵抗
Meijing Wang1, Ben M Tsai, Paul R Crisostomo
1Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Circulation
|July 6, 2006
概括
雌性小鼠在心脏缺血和再注血 (I/R) 后对瘤缩因子-α受体1 (TNFR1) 信号产生抵抗,有助于更好的恢复. 这种TNFR1信号传递的性别差异可能解释了女性的改善结果.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 心肌病理生理学 心肌病理生理学
背景情况:
- 瘤亡因子-α (TNF) 增加心肌缺血后和再输血 (I/R),导致功能障碍.
- 55kDa的TNF受体 (TNFR1) 可能会调解TNF的有害作用,但TNF也可以有益.
- 心力衰竭发生率和存活率的性别差异表明对TNF信号的反应是不同的.
研究的目的:
- 在I/R.期间调查心肌TNFR1信号传递中的性别差异.
- 为了测试女性心肌在缺血期间表现出TNFR1信号抵抗的假设.
主要方法:
- 野生类型 (WT) 和TNFR1-Knockout的雄性和雌性小鼠进行I/R的比较.
- 评估心肌功能,TNF诱导的抑郁和炎症标志物的表达.
- 对细胞因子信号蛋白3 (SOCS3) 的抑制剂I/R后表达的分析.
主要成果:
- 雌性WT小鼠比雄性表现出更好的血后复苏,这归因于TNFR1信号抵抗.
- 雌性WT小鼠在TNF输液后表现出较少的心肌抑郁.
- 在男性中,TNFR1 除改善了结果,但在女性中没有改善,女性在I/R后表达了更高的SOCS3水平.
结论:
- 在I/R之后的心肌TNFR1信号传递方面存在显著的性别差异.
- 女性的TNFR1信号抵抗,可能由SOCS3调解,有助于改善I/R后的心脏结果.
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