体外心脏震波通过调控内皮祖细胞PI3K/Akt/eNOS信号通路防治冠心病的分子机制研究

促血管新生是改善冠心病（CHD）患者心肌缺血的重要手段。课题组采用体外心脏震波（ECSW）治疗终末期CHD患者，发现能改善患者心功能、缓解心绞痛症状。为探究ECSW治疗CHD的作用机制，本课题组进一步研究发现ECSW能够促进CHD患者内皮祖细胞（EPCs）增殖，改善患者心肌灌注，抑制心室重构，且与调控心肌血管新生的PI3K/Akt信号通路密切相关。但ECSW调控EPCs PI3K/Akt信号通路及其下游靶点促心肌血管新生的机制尚未完全阐明。本项目将采用更接近CHD临床病理特征的EPCs缺氧模型和动脉粥样硬化动物心梗模型，从细胞和动物水平探讨ECSW对EPCs增殖、凋亡、迁移、粘附、归巢和血管形成的影响，揭示ECSW激活EPCs促血管新生功能，改善心肌缺血的作用机制与其调控PI3K/Akt/eNOS信号通路密切相关。通过项目研究，为ECSW临床治疗CHD提供科学依据。

An important mean to treat coronary heart disease (CHD) is to promote angiogenesis. Research has shown that extracorporeal cardiac shock wave (ECSW) can significantly improve the heart function of patients, relieve angina. In order to study the mechanism of ECSW treating coronary heart disease, Further study also found that ECSW can promote the proliferation of endothelial progenitor cells (EPCs), improve myocardial perfusion and inhibit ventricular remodeling of CHD patients which involving the signal pathway of modulating angiogenesis PI3K/Akt. However, the mechanism of ECSW in the treatment of CHD by activating EPCs function via the signal pathway PI3K/Akt/eNOS and downstream target have not yet been elucidated. The project intends to establish hypoxia EPCs models by APOE gene knockout rats in vitro and atherosclerotic myocardial infarction models in conformity with the clinical pathological features of CHD, We will discuss the effects of ECSW on EPCs proliferation, apoptosis, migration, adhesion and angiogenesis. Furthermore, we will also reveal ECSW activates EPCs angiogenesis function to improve myocardial ischemia via the signal pathway PI3K/Akt/eNOS. The study will provide evidence of the applications of ECSW in treatment of CHD.