相关实验视频
在心力衰竭中与异性瘤缩因子受体相关的重塑反应:核因子-kappaB和炎症激活的作用
Tariq Hamid1, Yan Gu, Roger V Ortines
1Institute Institute of Molecular Cardiology, Department of Medicine, University of Louisville and Louisville Veterans Affairs Medical Center, Louisville, KY 40202, USA.
Circulation
|March 4, 2009
概括
瘤亡因子-α (TNF) 受体1 (TNFR1) 恶化了心力衰竭 (HF) 的重塑,而TNFR2则改善了它. 这两种受体都会在高频率中导致腹功能障碍和氧化应激.
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
- 分子医学是分子医学.
背景情况:
- 临床前研究表明TNF中和有利于心力衰竭 (HF),但临床试验是负面的.
- 这项研究调查了TNF受体 (TNFRs) 在HF病变发生过程中的矛盾作用.
- 我们假设TNFR1和TNFR2在高频中具有不同的,相反的功能.
研究的目的:
- 阐明TNFR1和TNFR2在心脏重塑和心力衰竭期间的功能中的特定作用.
- 了解TNFR1和TNFR2在高频率中对TNF的反应中介导的差异信号通路.
- 为了帮助开发针对心力衰竭的针对性抗TNF疗法.
主要方法:
- 在野生型,TNFR1淘汰和TNFR2淘汰小鼠中使用冠状动脉结诱导心力衰竭.
- 评估了心脏重塑,亡,炎症,氧化应激和收缩功能.
- 分析了NF-kappaB,p38 MAPK和JNK2的激活,以及细胞因子的表达.
- 心肌细胞亡在体外使用H9c2细胞进行了研究.
主要成果:
- 与野生型HF小鼠相比,TNFR1淘汰小鼠显示出改善的心脏重塑,降低了细胞灭亡,并减少了炎症信号传递.
- TNFR2淘汰赛小鼠表现出加剧的心脏重塑,纤维化增加和炎症增加.
- 无论是TNFR1和TNFR2淘汰赛小鼠都显示出改善了透缩功能和减少了氧化应激.
- TNFR1信号促进了TNF诱导的心肌细胞亡,而TNFR2信号减弱了它.
结论:
- 在高血压中,TNFR1和TNFR2对心脏重塑,高血压,炎症和亡产生相反的影响.
- TNFR1信号加剧了不良的HF过程,而TNFR2信号改善了它们.
- 通过TNFR1和TNFR2进行综合信号传递对于高频率患者的透缩功能障碍和氧化应激是必要的.
- 针对高频率TNF的治疗策略必须考虑TNFR1和TNFR2.2的不同和对立的作用.
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