微血管损伤是放射性脑损伤（RBI）发生发展的核心环节，我们的前期研究已证实RBI后脑内血管内皮生长因子（VEGF）表达上调，但我们同时发现，上调的VEGF并不能增加新生血管，反而会引起血管生成素比率失衡造成血脑屏障损伤，其具体机制尚未完全阐明。多项研究证实了VEGF对调节性T细胞（Treg）的趋化作用，而新近研究表明，Treg可以通过分泌白介素-35（IL-35）抑制内皮功能，减少血管新生。由此我们提出：照射后脑内上调的VEGF是否可以从受损的血脑屏障外趋化Treg，增加IL-35的分泌，从而阻碍成熟血管生成。本项目拟检测RBI患者脑内血管调控分子、Treg和IL-35的动态水平及微血管状况；并通过动物模型和细胞模型，从炎性细胞、炎症因子、血管调控分子及转录因子等方面深入探讨RBI后微血管损伤的具体机制,进一步观察干预IL-35能否修复RBI后损伤的微血管，以期为RBI寻找新的治疗靶点。

Microvascular injury is the key of the onset and progression of radiation-induced brain injury (RBI). Our previous studies have confirmed that the expression of vascular endothelial growth factor (VEGF) up-regulated in RBI. However, we also find that the up-regulated VEGF does not increase neovascularization, but causes the imbalance of angiopoietin ratio and leads to the damage of blood-brain barrier. Its specific mechanism has not yet been fully elucidated. Many studies have confirmed the chemotactic effect of VEGF on regulatory T cells (Treg). Moreover, recent studies have shown that Treg can inhibit endothelial activation and reduce angiogenesis by secreting interleukin-35 (IL-35). Therefore, we suggest whether the up-regulated VEGF in the brain after irradiation can chemotactically recruit Treg through the damaged blood-brain barrier, increase the secretion of IL-35, and thus inhibit mature angiogenesis. This project aims at detecting the dynamic levels of VEGF, Treg, IL-35 and microvascular situation in the brain of RBI patients, and exploring the specific mechanism of microvascular injury after RBI in terms of inflammatory cells, inflammatory factors, vascular regulatory molecules and transcription factors in animal and cell models. In order to find a new therapeutic target for RBI, we would further observe whether IL-35 can repair the damaged microvessels after RBI.