基于ACE2-Ang(1-7)-Mas轴探讨定心方对动脉粥样硬化易损斑块稳定性的干预机制

The rupture and hemorrhage of vulnerable plaque is the leading cause of acute cardio-cerebro-vascular events. Through the western medicine could stabilize atherosclerotic plaque in some degree,the danger of acute case still exists. Clinical trials have identified that Dingxin Recipe has a scientific effect in coronary heart disease and arrhythmia. Animal experiments have shown that Dingxin Recipe could protect blood vessels; anti-inflammation; moderate blood lipids; anti-oxidant stress; alleviate atherosclerosis and stabilize plaque, but its mechanism still remains unknown. The web regulated by ACE2-Ang(1-7)-Mas axis, which shows similar effects with Dingxin Recipe, is closely related to the stability of vulnerable plaque. We suppose that Dingxin Recipe could stabilize atherosclerotic plaque through modulating the web regulated by ACE2-Ang(1-7)-Mas axis. The aim of this study is to explore the molecular mechanism of Dingxin Recipe and ACE2-Ang(1-7)-Mas axis in vulnerable plaque in rabbit model and reveal the target point of Dingxin Recipe in cell level.

易损斑块的破裂出血是引起急性心脑血管事件的主因，目前的西医治疗手段仍然存在问题。中药定心方经多年临床实践证实对冠心病及心律失常疗效显著，并可预防心肌梗死。动物实验表明定心方能稳定斑块，但其具体机制尚需明了。ACE2-Ang(1-7)-Mas轴调控网络与斑块稳定性关系密切，其抗炎、血管保护、抗氧化应激等作用与定心方类似，我们认为定心方可能通过ACE2-Ang(1-7)-Mas轴调控网络稳定易损斑块。因此本项目从ACE2-Ang(1-7)-Mas轴着手，拟建立易损斑块家兔模型，研究定心方对易损斑块稳定性的干预效用；在细胞水平采用三维细胞培养体系和基因转染技术，从信号通路方面探讨定心方对ACE2-Ang(1-7)-Mas轴的调控机制。通过整体和离体水平研究明确ACE2-Ang(1-7)-Mas轴在易损斑块中的作用机理，进一步揭示定心方干预易损斑块机制及具体作用靶点，为冠心病的防治研究提供新思路。

易损斑块的破裂出血是引起急性心脑血管事件的主因，在动脉粥样硬化的发生发展中起着重要的作用，但是目前的西医治疗手段仍然存在问题。中药复方定心方经过多年临床实践证实对冠心病及心律失常疗效显著，并可预防心肌梗死。动物实验表明定心方能够稳定斑块，但其具体机制尚需明了。ACE2-Ang(1-7)-Mas轴调控网络与斑块稳定性关系密切，其抗炎、血管保护、抗氧化应激等作用与定心方类似，因此我们认为定心方可能通过ACE2-Ang(1-7) -Mas轴调控网络稳定易损斑块，从而发挥抗AS的作用。因此本项目从ACE2-Ang(1-7)-Mas轴着手，拟应用ApoE基因敲除小鼠喂饲高脂饲料的方法制作AS模型，研究定心方对易损斑块稳定性的干预效应；同时应用ox-LDL诱导的人脐静脉内皮细胞作为细胞模型，分别从体内和体外两个方面探讨定心方对ACE2-Ang(1-7)-Mas轴的调控机制。通过整体和离体水平明确ACE2-Ang(1-7)-Mas轴在易损斑块中的作用机理，进一步揭示定心方干预易损斑块的机制及具体作用靶点，为动脉粥样硬化的防治研究提供新思路。