心肌梗塞扩张和矩阵金属蛋白酶抑制
Rupak Mukherjee1, Theresa A Brinsa, Kathryn B Dowdy
1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Circulation
|February 5, 2003
概括
矩阵金属蛋白酶抑制 (MMPi) 减少了心肌梗塞 (MI) 后的左心室 (LV) 扩张和心脏病扩张. MMPi还调节了受影响心脏区域的特定MMP和MMP组织抑制剂 (TIMP) 水平.
科学领域:
- 心血管研究研究心血管研究
- 进行心脏重塑.
- 药理干预药理干预
背景情况:
- 心肌梗塞 (MI) 后的左心室 (LV) 重塑可能涉及矩阵金属蛋白酶 (MMP) 激活.
- 研究MMP抑制 (MMPi) 提供了一个潜在的治疗策略.
研究的目的:
- 为了评估MMP抑制对心肌梗塞后区域LV几何学的影响.
- 评估MMP和MMPs组织抑制剂 (TIMP) 水平在MMPi的MI后的变化.
主要方法:
- 在诱导心脏病发作后,使用带有放射性不透明标记物的猪来测量区域心肌几何状况.
- 向MI后的猪给予MMPi (PD166793) 或安慰剂,并在2周和8周内评估结果.
- 测量了 LV 尺寸,心脏病发作大小,MMP 活性和 TIMP-1 水平.
主要成果:
- 在MI后8周,MMPi显著减弱了LV的终端透析维度,并减少了区域性心脏病发作区域,与仅患有MI的组相比.
- 活体MMP的蛋白质分解活性被MMPi降低.
- 在MI区域,MMPi使膜型MMP水平正常化,并增加TIMP-1水平.
结论:
- 在MI愈合的晚期阶段,MMP抑制有效地减弱了LV扩张和心脏病扩张.
- 外源性MMPi证明了MMPs和TIMPs的特定区域调制.
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