在渐进性心力衰竭的老鼠模型中,矩阵金属蛋白酶抑制减弱了左心室重塑和功能障碍
J T Peterson1, H Hallak, L Johnson
1Departments of Cardiovascular Pharmacology, Pfizer Global Research and Development, Ann Arbor, Michigan, USA. tom.peterson@pfizer.com
Circulation
|May 23, 2001
概括
在动物心力衰竭模型中,矩阵金属蛋白酶 (MMP) 抑制显著减少左心室 (LV) 扩张和改善功能. 这表明MMP在心脏功能障碍的进展中起着关键作用.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 矩阵金属蛋白酶 (MMP) 激活与疾病期间的组织重塑有关.
- 增加的MMP活性是左心室 (LV) 衰竭进展的已知因素.
- 这项研究调查了MMP抑制在预防LV重塑和功能障碍方面的治疗潜力.
研究的目的:
- 测试抑制MMPs会影响LV重塑和功能发展LV衰竭的假设.
- 在动物模型中评估一种特定的MMP抑制剂 (PD166793) 对心脏结构和性能的影响.
主要方法:
- 使用自发高血压心力衰竭 (SHHF) 的老鼠和正常血压的Wistar-Furth (WF) 的老鼠.
- 在不同年龄 (9个月和13个月) 的未经治疗的SHHF大鼠,MMP抑制剂治疗的SHHF大鼠和WF大鼠中比较LV大小和功能.
- 测量了LV峰值+dP/dt,LV体积,以及体外LV心肌MMP-2活性.
主要成果:
- 与WF大鼠相比,SHHF大鼠在13个月内表现出减少的LV功能 (下峰+dP/dt) 和增加的LV扩张.
- 在SHHF大鼠中,LV心肌MMP-2活性显著升高 (约2倍).
- 与未经治疗的SHHF大鼠相比,MMP抑制在SHHF大鼠中使LV峰值+dP/dt正常化,LV体积显著降低.
结论:
- 在这种动物模型中,MMP活性是 LV 扩张和心力衰竭进展的重要因素.
- 直接抑制MMP通过减轻心脏重塑和功能障碍,证明了治疗效益.
- 准MMP代表了管理心力衰竭的潜在策略.
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