血脑屏障破坏与氨基酸兴奋性毒性是导致脑出血（ICH）后继发性脑损伤的重要因素。有关报道及我们的预实验结果提示Annexin A1与Annexin A7可能参与到血脑屏障及谷氨酸引起的神经兴奋性毒性的调节中。本研究着重探索Annexin A1与Annexin A7在脑出血后继发性脑损伤中的作用。第一部分围绕细胞层面展开，在ICH体外模型中，通过基因定点突变和基因调控，结合transwell、电镜、高效液相色谱以及电生理技术，了解单层内皮细胞屏障作用和神经元兴奋性毒性的变化；第二部分围绕组织层面展开，通过活体脑片膜片钳技术，结合基因调控，评估电生理变化；第三部分围绕活体动物ICH模型展开，应用转基因和基因调控等方法，观察血脑屏障通透性和神经兴奋性毒性的变化。本研究纵向从细胞、组织和活体三个层面，横向从超微结构、电生理和分子生物学三个层面开展研究，将为改善 ICH 预后提供新思路和理论依据。

Blood-brain barrier (BBB) damage and excitatory amino acids toxicity after intracerebral hemorrhage (ICH) are important factors affecting the prognosis of ICH patients. The mechanism is unknown at present. There is a wealth of evidence suggesting that Annexin A1 and Annexin A7 may participate in the regulation of BBB permeability and excitatory amino acids toxicity. This project focused on exploring the roles of Annexin A1 and Annexin A7 in ICH-induced secondary brain injury. Firstly, we try to discover the mechanism at a cellular level. Gene transfection and RNAi are used to regulate the target genes expression, and then transwell assay, electron microscopy, high performance liquid chromatography, and patch-clamp technique were used to assess the changes in the phosphorylation of target proteins, BBB permeability and excitatory amino acids toxicity. Secondly, in brain slice from different genetic backgrounds, we use patch-clamp technique to study electrophysiological characteristics change. Finally, ICH model is established in transgenic mice and drug treated rats, and then we observe the changes of BBB permeability, excitatory amino acids toxicity, and assess the neurologic scoring. The longitudinal studies from three levels of cell, tissue and in vivo, horizontal researches from three levels of ultrastructure, electrophysiology and molecular biology in this study will provide us new ideas and theoretical basis to improve the prognosis of ICH.