血管新生是肝硬化门静脉高压发生发展重要的病理生理学基础，内脏高动力循环和门体侧支血管形成受VEGF等多种促血管生长因子调控，以抗血管生成为目标的分子靶向治疗有望成为预防或治疗门静脉高压的新方法。内皮抑素是目前已知作用最强、效果最好的血管生成抑制因子。本项目建立门静脉高压大鼠模型，在不同时间点检测内脏、肝脏组织内皮抑素表达水平的动态变化和空间分布特征；并以门静脉高压形成的不同时间点，采用内皮抑素腺病毒过表达载体予以干预，检测大鼠内脏、肝脏组织新生血管数量、门体侧支分流率、血管生成相关因子表达水平等，探讨门静脉高压形成过程中，内皮抑素在内脏高动力循环和门体侧支血管形成中的作用，观察内皮抑素在门静脉高压形成不同阶段抗血管生成治疗、缓解门静脉高压的作用，并研究其分子机制。本研究将揭示内皮抑素参与门静脉高压血管新生的分子机制，为分子靶向治疗提供研究基础。

Angiogenesis is a physiopathologic hallmark of liver cirrhosis that is essential to develop and maintain portal hypertension, splanchnic hyperaemia and portosystemic collateralisation. VEGF-dependent angiogenesis plays a crucial part in this process, which means anti-angiogenic targeted therapy could be a new method for prevention or treatment of portal hypertension. Endostatin is one of the strongest and best angiogenesis inhibiting factor. In the present study, endostatin expression profiling in the internal organs and liver tissue was determined in animal models at different time points. The ability of exogenous endostatin overexpression by adenovirus-mediated gene transfer to inhibit angiogenesis, portosystemic shunting and expression of angiogenesis related factors were evaluated. The effect of endostatin in the development of splanchnic hyperaemia and portosystemic collateralisation, as well as the role of overexpression of exogenous endostatin for the treatment of anti-angiogenic targeted therapy and portal hypertension were also evaluated. The purpose of the present study was to reveal the role of endostatin in the angiogenesis process during portal hypertension and provide the research basis for molecular targeted therapy.