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缺血预调可以通过升调抗死亡基因Bcl-2来降低细胞亡
N Maulik1, R M Engelman, J A Rousou
1Department of Surgery, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA. nmaulik@panda.uchc.edu
Circulation
|November 24, 1999
概括
缺血预先调节通过激活NF-kappaB和调节Bcl-2来保护心脏,其中涉及活性氧物种. 这一过程减少了心肌细胞亡和心肌梗塞.
科学领域:
- 心血管研究研究心血管研究
- 分子心脏病学分子心脏病学
- 细胞信号传输 细胞信号传输
背景情况:
- 缺血性转流损伤导致心肌细胞亡和Bcl-2基因下调.
- 缺血预条件 (PC) 通过氨酸激酶,p38 MAP激酶和NF-kappaB信号减少了细胞亡.
- 由于NF-kappaB的敏感性和BCL-2的抗氧化作用,反应性氧物种 (ROS) 有关.
研究的目的:
- 调查反应性氧物种和NF-kappaB在缺血预调的保护性信号通路中的作用.
- 确定ROS和NF-kappaB是否通过PC调解了心肌细胞亡和心肌梗塞的减少.
主要方法:
- 孤立的老鼠心经历了缺血/再输血,有或没有基清除剂 (DMTU) 或NF-kappaB阻断剂 (SN50).
- 预先条件包括在持续的全球性缺血和再输血之前重复出现短暂的缺血/再输血发作.
- 评估了肌酸激酶释放,甲,心脏病发作大小,亡,DNA碎片化,NF-kappaB激活和Bcl-2表达.
主要成果:
- PC显著降低了心肌梗塞和心肌细胞亡.
- 通过DMTU和SN50.0,PC的心脏保护作用被消除了.
- PC上调调节了Bcl-2,这种效果被DMTU和SN50部分阻.
- 缺血/再输和PC都激活了NF-kappaB,在PC心脏中具有更高的活性;DMTU和SN50阻止了这种激活.
结论:
- 活性氧物种对于涉及NF-kappaB的PC介导信号传导至关重要.
- 通过PC激活NF-kappaB的程度高于简单的缺血/再输,与减少的亡相关.
- 抗氧化基因Bcl-2的升调与PC实现的心肌细胞亡的减少相反相关.
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