蛛网膜下腔出血（SAH）后早期脑损伤是导致神经功能障碍的主要原因，血脑屏障破坏是其级联损伤的首要环节。由紧密连接蛋白(TJPs)构成的紧密连接是血脑屏障的结构和基础，SAH后紧密连接蛋白降解可导致血脑屏障的破坏。我们的前期研究发现，激活肌细胞增强因子2D（MEF2D）能抑制血脑屏障破坏，减轻神经损伤。文献表明，MEF2D能激活Krüppel样转录因子4（KLF4），而后者能够促进肿瘤血管内皮细胞上TJPs的表达。进一步的预实验发现，MEF2D在脑血管内皮细胞上存在表达，并与KLF4基因启动子区相互作用。据此我们提出假说：MEF2D通过激活KLF4，在SAH后上调TJPs表达。本课题拟从体内外两个层面，通过RNA干扰，MRI扫描，跨细胞电阻测量等技术研究MEF2D通过激活KLF4上调血管内皮细胞上TJPs的表达，减轻血脑屏障的破坏、改善神经损伤的作用，为临床治疗SAH提供新靶点和理论依据。

Early brain injury caused by subarachnoid hemorrhage (SAH) is the main risk of neurological deficits, and blood-brain barrier disruption is the first step in this cascade of damage. Tight junctions, which are formed by tight junction proteins (TJPs), constitute the structure and foundation of blood brain barrier. Degradation of TJPs after SAH can lead to disruption of blood-brain barrier. Our previous study found that the activation of myocyte enhance factor 2D (MEF2D) could protect blood-brain barrier from disruption and alleviate neurological deficits. A former literature shows that MEF2D could activate Krüppel-Like Factor 4 (KLF4), and the latter could promote the expression of TJPs in cancer endothelial cells. Our further experiments found that MEF2D was expressed in brain endothelial cells, and it could interact with KLF4 gene’s promoter region. Therefore, we provide the hypothesis that MEF2D could up-regulate the expression of TJPs by activating KLF4 after SAH. In this research, we will use multiple techniques such as RNA interference, MRI scanning and trans-endothelial electric resistance assay to uncover the effect and mechanism of MEF2D’s function in up-regulating TJPs expression by mediating KLF4, protecting blood-brain barrier from disruption and alleviating neurological deficits after SAH in vivo and in vitro, so as to provide new targets and theory basis in SAH management.