心肌缺血再灌注血管内皮损伤PKG/VASP的修复机制及灯盏花乙素的干预作用

血管内皮损伤与心肌缺血再灌注（IR）的发生发展密切相关，减轻和修复血管内皮损伤成为防治心肌IR损伤的一个新方向。蛋白激酶G（PKG）/血管扩张刺激磷蛋白（VASP）通路在调节血管内皮功能中有重要作用，但PKG/VASP通路在心肌IR血管内皮损伤中的修复机制尚未完全阐明。本项目拟建立人心脏微血管内皮细胞、大鼠离体冠状动脉和在体心肌IR模型，从细胞分子、离体血管和整体动物水平，探讨PKG/VASP对IR所致血管内皮损伤的修复机制，并明确其下游ERK靶点。此外，由于我国应用中药治疗冠心病的特点，本项目将探讨中药灯盏花乙素（SCU）干预对PKG/VASP拮抗心肌IR血管内皮损伤的影响。本项目的实施，将明确PKG/VASP在心肌IR血管内皮损伤中的保护作用及其分子机制，为心肌IR损伤的防治提供新的作用靶点；并阐明SCU在防治缺血性心血管病方面的分子靶点及作用机制，为SCU的临床合理用药提供科学依据。

The endothelium is a major determinant of the capacity of tissue to recover from ischemia reperfusion (IR), and interventions capable of protecting the endothelium from IR are of direct clinical interest. Protein kinase G (PKG)/Vasodilator-stimulated phosphoprotein (VASP) pathway holds significant importance for endothelial barrier properties during hypoxia, and it is crucially important for myocardial IR injury. However, PKG/VASP protects against endothelium dysfunction induced by myocardial IR and its mechanisms have not yet been elucidated. In this research,three models will be used: a rat model of myocardial IR, an isolated coronary artery hypoxia reoxygenation (HR) model, and a human cardiac microvascular endothelial cell HR model. We will evaluate the molecular mechanism of the protective effects of PKG/VASP on myocardial IR-induced endothelium dysfunction, and the role of the PKG/VASP/ERK pathway. Furthermore, we will examine the effects of scutellarin (SCU), a Chinese traditional medicine, protects against myocardial IR–induced endothelium dysfunction, and whether the protection is mediated by the PKG/VASP pathway. The study will provide a promising target for the treatment of myocardial IR and a new mechanism to explain the cardiovascular protective effects of SCU.