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先进糖化终端产品的受体:肌肉心脏缺血损伤的关键调节器
Loredana G Bucciarelli1, Michiyo Kaneko, Radha Ananthakrishnan
1Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Circulation
|March 1, 2006
概括
先进糖化终产品 (RAGE) 的受体在缺血/再生 (I/R) 损伤后的心脏损伤中起着关键作用. 阻断RAGE可以保护心脏免受I/R损伤,并改善恢复.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 细胞损伤机制 细胞损伤机制
背景情况:
- 重灌疗法受到先前存在的缺血损伤的限制.
- 了解心脏细胞死后缺血/再输血 (I/R) 机制对于开发干预措施至关重要.
- 先进糖化终产品 (RAGE) 的受体正在研究其在心肌I/R损伤中的作用.
研究的目的:
- 测试RAGE是肌肉心脏I/R损伤的关键调节器的假设.
- 调查RAGE在I/R期间对心脏功能和新陈代谢的影响.
- 探索针对I/R损伤中的RAGE的治疗潜力.
主要方法:
- 在缺血性大鼠心脏中评估RAGE和连接体表达.
- 在老鼠中作为预治疗,给予可溶性RAGE (sRAGE).
- 使用RAGE-null小鼠专门评估RAGE在I/R中的作用.
- 测量了心脏功能,乳酸脱酶 (LDH) 释放和腺三酸盐 (ATP) 水平.
- 分析了可诱导的氧化合成酶 (iNOS),氧化,循环氨酸单酸盐 (cGMP) 和氨酸水平.
主要成果:
- 在缺血性大鼠心脏中,RAGE及其连接物显著上调.
- 在大鼠中,sRAGE预治疗减少了缺血损伤和改善了心肌功能.
- RAGE-null小鼠对I/R损伤表现出显著的保护,心脏功能和ATP水平得到改善.
- 在这两种物种中,RAGE激活与增加的iNOS,氧化,cGMP和尼托铁相关.
结论:
- 愤怒在调解心肌的I / R损伤方面发挥着关键作用.
- 针对RAGE轴提供了减少I/R损伤的潜在治疗策略.
- 与高级糖化终产品的RAGE相互作用会影响心肌肌肉能量代谢和I/R期间的功能.
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