血管内皮生长因子（VEGF）过表达是放射性脑损伤（RBI）病程中的突出表现。与传统认识相反，VEGF非但不能修复血管，反而加重微血管损伤促使RBI发生发展，目前具体机制尚不清楚。新近研究发现血管生成调控通路Ang/Tie-2中Ang2/Ang1的比率增加引起血管异常重塑，肿瘤高水平的VEGF对Ang2有上调作用。由此我们提出RBI发病的新机制：照射后VEGF过表达上调Ang2水平促使微血管异常重塑，阻碍血管生成。本项目拟检测RBI患者脑组织VEGF、Ang-1、Ang-2的失衡情况及微血管的破坏；并通过动物模型和细胞模型，研究脑组织照射后上述调控分子水平变化、微血管形态和功能指标改变，及彼此间的相关关系，以阐明VEGF过表达促使RBI发病的机理。进一步采用VEGF拮抗剂干预、基因敲入和siRNA干扰技术，探讨可否通过降低VEGF水平而减轻微血管异常重塑，为治疗RBI寻找有效方法。

Overexpression of Vascular endothelial growth factor (VEGF) is an outstanding manifestation in the course of radiation-induced brain injury (RBI). Contrary to the conventional wisdom, far from repairing the damaged vessel, VEGF actually accelerates the vascular destruction, which would prompt the occurrence and development of RBI. For now, the specific mechanism is not very clear. Recent studies found that the increased ratio of Ang2/Ang1 in the angiogenesis regulatory pathway Ang/Tie-2 can result in abnormal vascular remodeling. And the high-level expression of VEGF in tumor can up-regulate angiopoietin-2. Thus, we propose a novel mechanism on the onset of RBI: After exposuring to the ionizing radiation, VEGF overexpression up-regulates Angiopoietin-2 and causes abnormal microvascular remodeling, which would impede normal angiogenesis. The project intends to investigate the imbalance of angiogenesis factors(such as VEGF、Ang-1 and Ang-2) and the microvascular damage in the brain tissue of RBI patients. In the animal model and cell model, in order to clarify the mechanism that VEGF overexpression prompt the onset of RBI , we plan to study the changes in the levels of these angiogenesis regulatory molecule and in the microvascular morphologic and functional indicators after irradiation in the brain tissue, and investigate the interaction between each other. By using the VEGF antagonist、gene knock-in and siRNA technology, we further explore whether the decreasing of VEGF levels reduce the abnormal microvascular remodeling. This study will help to find out a new effective therapeutic method of RBI.