丹参调控Ang-2/Tie2轴促进肿瘤和缺血性疾病血管正常化

肿瘤与缺血性疾病新生血管均为未成熟的非功能性血管，血管正常是肿瘤和缺血性疾病治疗的关键。肿瘤和缺血性疾病都有血瘀病机，活血化瘀法是临床常用治法，其中丹参用药频率很高。课题组前期发现，丹参使肿瘤和缺血性疾病新生血管趋于正常化。而Ang-2/Tie2信号轴介导血管重塑和新生血管网成熟，干预血管正常化。故提出假说：丹参通过干预Ang-2/Tie2信号轴活化促进肿瘤和缺血性疾病血管正常化，从而用于治疗这两种疾病。.拟用计算机辅助筛选结合实验，筛出与Ang-2具潜在结合能力的丹参有效成分，构建三维立体动态可视化体外血管正常化研究平台，采用肿瘤模型、缺血性模型和二者共患病模型，对不同疾病状态血管正常化相关指标进行验证，并利用正/反向实验手段剖析对Ang-2/Tie2信号轴调控作用及机制，探讨丹参对肿瘤和缺血性疾病血管正常化的关键作用环节和调控方式，为临床应用提供实验依据，并探索血管正常化的治疗模式。

Tumor and ischemic disease neovascularization are immature non-functional blood vessels, normal blood vessels are the key to the treatment of tumor and ischemic diseases. Since tumor and ischemic diseases have blood stasis pathogenesis, promoting blood circulation and removing blood stasis is a common clinical treatment, in which salvia miltiorrhiza drug frequency is very high. In our early research, Salvia miltiorrhiza normalized the neovascularization of tumors and ischemic diseases. Ang-2/Tie2 signaling axis mediates vascular remodeling and neovascularization, and interferes with vascular normalization. Therefore, it is hypothesized that Salvia miltiorrhiza can promote the normalization of blood vessels in tumor and ischemic diseases by interfering with the activation of Ang-2/Tie2 signaling axis, so as to be used in the treatment of these two diseases..It is proposed to use computer-assisted screening and binding experiments to screen out the active components of Salvia miltiorrhiza with potential binding ability to Ang-2. The three-dimensional dynamic visualization of the in vitro vascular normalization research platform was constructed. The tumor model, the ischemic model and the comorbidity models were used to verify the relevant indicators of vascular normalization in different disease states. Besides, the positive and negative experimental methods were used to analyze the regulation and mechanism of Ang-2/Tie2 signaling axis, and the key action links and regulation methods of Salvia miltiorrhiza on vascular normalization of tumor and ischemic diseases were discussed, which provide experimental basis for clinical application and explore the treatment modalities of vascular normalization.