脑缺血后血脑屏障通透性增加可能与VE-cadherin复合体的解离有关，但其调节机制不是很清楚。我们前期预实验发现，Annexin A2参与了脑缺血后血脑屏障通透性的增加并和VE-cadherin存在着相互作用。根据文献及我们预实验，我们提出假设：Src等激酶能促使Annexin A2磷酸化，导致VE-cadherin的磷酸化或内化，从而导致VE-cadherin复合体的解离，这是脑缺血后血脑屏障通透性增加的主要原因之一。我们拟利用Annexin A2基因敲除及转基因小鼠，RNA干扰与过表达以及蛋白质谱等技术从整体、细胞和分子水平上对以上假设进行验证。本课题的完成，将进一步深入认识Annexin A2在VE-cadherin复合体解离中的作用，并利用重组Annexin A2及其拟似物，或通过调节Annexin A2的磷酸化来调节VE-cadherin复合体解离，为进一步的药物开发提供基础。

The increase of blood-brain barrier permeability after cerebral ischemia may be related to the dissociation of VE-cadherin-based compex, but the mechanism is not clear. Our preliminary data demonstrated that Annexin A2 participated increasing BBB permeability after cerebral ischemia and interacted with VE-cadherin. From other’s and our pilot works, we propose a hypothesis: Src kinase can induce Annexin A2 phosphorylation, leading to VE-cadherin phosphorylation or internalization, then leading to the dissociation of VE-cadherin-based complex, which is one of the main reasons for the increase of BBB permeability after cerebral ischemia. In this project, Annexin A2 knockout and transgenic mice, RNA interference and over-expression, protein mass-spectrometry technology were used to approve this hypothesis. From this project, it will help to know the role of Annexin A2 in the VE-cadherin –based complex dissociation, and by using recombinant Annexin A2 or its analogues, or regulating Annexin A2 phosphorylation for VE-cadherin-based complex dissociation, which is helpful for drug discovery in the further.