研究证实脑微血管内皮细胞内肌动蛋白聚合，张力纤维的形成是脑缺血再灌注损伤后血脑屏障破坏的始动因素。新近研究发现线粒体参与细胞内肌动蛋白骨架重组及再分布，线粒体功能障碍导致ATP产生减少或Ca摄取异常均会抑制F-actin解聚。因此维持血管内皮细胞中线粒体结构和功能稳态是保护血脑屏障完整性的新的治疗策略。大量研究证实HSPB8通过保护线粒体发挥神经保护作用，同时越来越多的证据表明HSPB8介导选择性自噬。因此我们推测，脑缺血再灌注后，HSPB8可能通过促进线粒体的自噬途径降解维持线粒体稳态。通过对线粒体的质量控制，进而促进F-actin解聚，实现其保护BBB完整性的作用。本课题中我们将采用体外培养BBB模型及大鼠MCAO/R模型，利用基因及药物干预的方法系统评价HSPB8在脑缺血/再灌注损伤中对血脑屏障结构和功能的保护作用，探讨其可能的机制，为缺血性卒中的治疗提供新的理论依据及干预靶点。

Ischemia/reperfusion-induced BBB impairment is initiated by subtle actin cytoskeletal rearrangement in brain microvascular endothelial cells(BMECs), thereby increasing their vulnerability to attack by MMPs from infiltrating immune cells. Prevention of early cytoskeletal changes in microvascular ECs could attenuate BBB breakdown and secondary tissue injury, and therefore ameliorate long-term neurological deficits. Actin turnover appears to be critically dependent on proper maintenance of mitochondrial ATP production. Indeed, severe reduction in ATP levels can cause massive increases in the concentration of dephosphorylated ADF family proteins, and these can form relatively massive cofilin-G-actin complexes that can severely attenuate actin turnover. Additionally, mitochondrial Ca2+ uptake controls actin cytoskeleton dynamics. Mitochondrial Ca2+ homeostasis deregulation leads to F-actin fibers accumulation. Therefore, maintaining mitochondrial function is supposed to be essential for F-actin depolymerization. Selective autophagy of mitochondria, known as mitophagy, is a fundamental process critical for maintaining healthy mitochondrial function through eliminating damaged mitochondria. HSPB8 is well known to facilitate the degradation of misfolded proteins linked to neurodegenerative disorders. Moreover, accumulating evidence support mitochondria as a selective target for HSPB8 mediated protection against a variety of stresses. Based on these findings, it is reasonable for us to hypothesize that HSPB8 may maintain mitochondrial homeostasis through mitophagy. Through degrading dysfunctional mitochondial, HSPB8 could restore mitochondrial function, and subsequently promote F-actin disassembly. Via regulating actin reorganization in BMECs, HSPB8 may attenuate BBB breakdown, and thus ameliorate neurological deficits. In this study, we used rat BMVECs subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) and rats exposed to transient middle cerebral artery occlusion/reperfusion (MCAO/R) to determine the protective potential of HSPB8 on BBB integrity and the mechanism underlying its protection.