基于HIF-1/VEGF/Notch轴研究丹参调控不同病理状态下血管生成的机制

丹参临床在心肌缺血和肿瘤中都有广泛应用，但在二者治疗中的作用截然不同：心肌缺血中，丹参能促进缺血组织血管生成；在肿瘤中，丹参能抑制肿瘤血管生成。为什么会产生这种现象？综观文献发现，二者血管生成都与缺氧诱导HIF-1/VEGF通路有关。因此推测：在心肌缺血与肿瘤两种不同病理状态下，丹参通过HIF-1/VEGF/Notch轴对血管生成表现出不同的调控作用。项目拟通过虚拟分子对接，找出对血管生成HIF-1/VEGF/Notch通路上影响显著的组分；运用A549肺癌模型和心肌缺血模型确认丹参对不同状态下血管生成的影响；考察丹参多组分对不同状态血管生成过程中芽生、管腔形成的影响；并采用Western Blot、Real-time PCR等现代生物技术考察丹参多组分对血管生成分子HIF-1/VEGF/Notch等影响，诠释丹参影响不同状态下血管生成的分子机制，为丹参的临床应用提供实验依据。

Salvia has different effect on myocardial ischemia and tumor. Salvia can promote angiogenesis in myocardial ischemia, but inhibit tumor angiogenesis. The effect of Salvia on myocardial ischemia and tumor is different. Why phenomenon appears? After reading the extensive literature, we find that the angiogenesis of the two diseases is relevant to hypoxia inducing HIF-1/VEGF pathway. So we presume that in different state of myocardial ischemia and tumor, salvia shows different effect on angiogenesis Through HIF-1/VEGF/Notch axis. The components of salvia will be classified according to different mother nuclear structure. This project is to find out the components of salvia that have obvious effects on molecular of HIF-1/VEGF/Notch pathway of angiogenesis through molecular docking. The highly metastatic lung cancer A549 model and cerebral ischemia model will be used to confirm the effct of salvia on angiogenesis of different microenvironment. The effect of salvia multi-component on the angiogenesis process of sprouting and lumen formation will be investigated. Modern Biotechnology, such as Western-blot and Real-time PCR will be used to verify the different effect of salvia multi-component on molecular of HIF-1/VEGF/Notch pathway of angiogenesis. The molecular mechanism of salvia affecting angiogenesis will be showed in the end. It will provide experimental basis for clinical application.