缺血再灌注(I/R)后血脑屏障的破坏是影响缺血性脑卒中预后的重要因素，发生机制不明。我们的预实验结果提示：在I/R条件下，脑微血管内皮细胞(BMVEC)自噬对血脑屏障可能具有保护作用。为此，我们提出假说：BMVEC自噬通过抑制I/R引起的氧化应激损伤保护血脑屏障。为了验证该假说，我们首先在I/R体外模型中，通过自噬调节剂和siRNA技术调控BMVEC自噬水平，结合transwell技术，了解单层内皮细胞屏障作用改变; 第二，建立活体动物I/R模型，应用自噬调节剂和内皮特异基因敲除小鼠调控BMVEC自噬水平，结合Evans blue染色，观察血脑屏障完整性的变化。第三，利用western blot、免疫荧光染色、DHE染色和siRNA技术，在体内外分析BMVEC自噬影响I/R条件下血脑屏障完整性的作用机制。本研究从分子、细胞、组织以及动物等多层次展开，将为改善I/R预后提供新思路和理论依据。

Blood-brain barrier damage after ischemia/reperfusion (I/R) is an important factor affecting the prognosis of ischemic stroke patients. The mechanism is unknown at present. There is a wealth of evidence suggesting that a moderate level of autophagy could protect vascular endothelial cells against environmental stress, such as starvation and oxidative stress. This project focused on exploring the roles of brain microvascular endothelial cell (BMVEC) autophagy in the integrity of blood brain barrier after I/R. Firstly, we try to discover the mechanism at a cellular level. Small molecule regulators of autophagy and RNAi are used to regulate the level of BMVCE autophagy, and then Transwell assay is used to assess the changes in endothelial barrier function. Secondly, I/R model is established in drug treated rats and mice with endothelial-specific deletion of Atg7, and then we observe neurologic scoring, brain water content and blood brain barrier permeability by Evans blue staining. Finally, by western blot, immunofluorescence staining and DHE staining, we study the mechanisms accounting for the effects of BMVEC autophagy on the integrity of blood brain barrier in vitro and in vivo. This study from multi-level of molecules, cells, tissues and animals will provide us new ideas and theoretical basis to improve the prognosis of ischemic stroke patients.