后血性收缩功能障碍的多巴胺治疗迅速诱导依赖的前性信号传递
Christof Stamm1, Ingeborg Friehs, Douglas B Cowan
1Department of Cardiac Surgery, Children's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
Circulation
|October 2, 2002
概括
多巴胺治疗改善了缺血后的心脏收缩性,但通过依赖的通路和线粒体损伤显著增加了心肌细胞亡. 这突显了在心脏病后心脏病护理中的关键权衡.
科学领域:
- 心脏病学 心脏病学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 缺血和上腺刺激可以诱导心肌细胞亡.
- 多巴胺是一种常见的甲基荷胺,可以通过信号传递增强收缩功能障碍后缺血的亡.
研究的目的:
- 为了调查多巴胺是否在后缺血收缩功能障碍模型中增加心肌细胞亡.
- 阐明依赖信号级联在多巴胺诱导的亡中的作用.
主要方法:
- 隔离的子心经经历了缺血-再输血.
- 用多巴胺治疗心脏,用MgATPase抑制剂 (BDM) 治疗多巴胺,或使用敏感化异型物 (ORG 30029).
- 使用TUNEL,PARP裂变,酶激活和Bax/Bcl-2表达来评估亡;测量细胞内.
主要成果:
- 缺血-再输液导致功能障碍,但没有显著的亡或亡.
- 多巴胺改善了收缩性,但显著增加了心肌细胞亡 (32.5±9对 5.5±1.6/1000核).
- 多巴胺提升了细胞内,激活了caspases (-3, -9),增加了Bax,并降低了Bcl-2. BDM和ORG 30029以不同的方式调节了这些效应.
结论:
- 对于收缩功能障碍的缺血后多巴胺治疗激活了亲亡信号传递.
- 这种激活可能是由依赖的过程和线粒体损伤介导的.
- 多巴胺的前性作用与其对收缩能力的有益作用不同.
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