基于血管生成微环境探讨理冲汤调控Ang/Tie-2信号传导通路抑制子宫肌瘤的作用机制研究

The local tumor microenvironment changes are important factors to promote the angiogenesis，which play a key role in the pathogenesis of uterine leiomyoma，the process is affected by angiopoietin signal transduction pathway（Ang/Tie-2 Pathway）regulation.Our previous studies found that Nourishing Healthy Qi and Eliminating Blood Stasis Chinese Medicine 'Lichong decoction' can inhibit the angiogenesis of uterine leiomyoma，suggesting that the mechanism of its anti-fibroids angiogenesis is related to the blocking of Ang/Tie-2 Pathway and the regulation of angiogenic microenvironment. In this project，we established the animal model of uterine leiomyoma ，using Micro-CT，vascular immunofluorescence technique to observe the Lichong decoction effect on angiogenesis in uterine leiomyoma microvascular 3D and 2D structure，at the same time to detect the expression of the related factors in the tumor microenvironment，confirm its effect on microenvironment of uterine leiomyoma.Then the use of uterine leiomyoma cells cultured in vitro technology to depth discussion the mechanism of its action，with methods used including transcriptome sequencing，MicroRNA screening，luciferase reporter gene，RNA interference methods and technologies，explorating the mechanism of inhibition of uterine leiomyoma of Lichong decoction from regulation of Ang/Tie-2 signal transduction pathway and improving the angiogenic microenvironment，riching the theory in TCM of 'vital qi deficiency and blood stasis' , guiding the clinical treatment of uterine leiomyoma.

肿瘤局部微环境变化是血管生成的重要促进因素，在子宫肌瘤的发病进程中起关键作用，该过程受血管生成素信号传导通路（Ang/Tie-2 Pathway）的调控。我们前期研究发现扶正祛瘀中药"理冲汤"对子宫肌瘤血管生成有抑制作用，推测其机制与调控血管生成微环境、阻断Ang/Tie-2 Pathway有关。本项目中，通过建立子宫肌瘤动物模型，采用Micro-CT、血管免疫荧光方法技术，观察理冲汤对子宫肌瘤微血管3D和2D结构的影响，并通过观察与肿瘤微环境相关的细胞因子的变化，确证其对子宫肌瘤微环境的改善作用。然后，运用子宫肌瘤细胞体外培养技术对其作用机制进行深入探讨，采用转录组测序、MicroRNA筛选、荧光素酶报告基因、RNA干扰等方法，探究理冲汤通过调控Ang/Tie-2 Pathway改善血管生成微环境进而抑制子宫肌瘤的作用机制，丰富中医"正虚血瘀"的理论，指导子宫肌瘤的临床治疗。