自发性脑出血（SICH）发病率高、起病急骤、致死致残率高，高血压是其主要发病原因之一，至今尚缺乏模拟临床SICH发病的动物模型。本课题组前期利用转基因技术，建立了条件诱导性cAMP 直接活化的交换蛋白1(EPAC1) 突变小鼠（EPAC1-/-小鼠），并将其与脑选择性表达血管紧张素II 的1型受体α（AT1α）小鼠（AT1α+/+小鼠）杂交，发现31%的EPAC1-/-/AT1α+/+ 小鼠出生后150±5天在基底节区出现脑出血灶、血压增高。本项目将在进一步研究该小鼠不同月龄时易损血管的重构变化特点；研究易损脑区内皮细胞及小胶质细胞的活性与功能变化特点；确定小胶质细胞-内皮细胞的信号交流的关键分子、及其在EPAC1-/-/AT1α+/+小鼠脑内血管重构中的作用。本项目建立的SICH转基因小鼠将为相关研究提供符合临床SICH发病的动物模型，为认识小胶质细胞-内皮细胞间的信号交流提供实验依据。

Spontaneous intracerebral hemorrahge (SICH) is a common disease with sudden onset and high rates of morbidity, mortality and disability. There is no animal model to simulate the process of SICH, which seriously constraints the studies of pathogenesis, drugs, early diagnosis and tissue repair of SICH. Previously, we established the conditionally EPAC1 (exchange protein 1 directly activated by cAMP) mutation mice (EPAC1-/- mice) and hybridizated them with AT1α+/+ mice (brain selected expressed angiotensin-1 receptor α mice). It was found that 31% EPAC1-/-/AT1α+/+ mice had hemorrhagic foci in the basal ganglia region and increased blood pressure at 150±5 days after birth. In this project we will further study the peak time, multiple brain regions and vulnerable vessels by magnetic resonance and morphologic techniques. The characteristic of the vulnerable vascular remodeling, activities and functions of microglia and endothelial cells in the vulnerable region, the key molecules acting as messengers between microglia and endothelial cells, and their roles in the vascular remodeling of EPAC1-/-/AT1α+/+ mice will be investigated. The research of this project will present a SICH model for related researches and be helpful for understanding the cross-talking between microglia and endothelial cells.