Cerebral ischemic stroke is regarded as one of the most serious diseases in the human central nervous system. The secondary ischemia and reperfusion (I/R) injury increased the difficulty of treatment. Moreover, the latent molecular regulating mechanism in I/R injury is still unclear. Based on our previous clinical study, we discovered that FK506 binding protein 5 (FKBP5) is significantly upregulated in patients, who suffered acute ischemic stroke (AIS), with high diagnostic value. Levels of FKBP5 were positively correlated with patients’ neurological impairments. Furthermore, a transient middle cerebral artery occlusion (tMCAO) model of mice was used to confirm that FKBP5 expression in plasma could reflect its relative level in brain tissue. Thus, we hypothesized that FKBP5 participated in the regulation of cerebral I/R injury. In order to explore the possible roles FKBP5 acted, the oxygen and glucose deprivation and reoxygenation (OGD/R) model was established to mimic I/R injury in vitro. FKBP5 expressing levels were changed by plasmid stable transfection. The altered expression of FKBP5 influenced cell viability and autophagy after OGD/R injury notably. Besides, AKT/FOXO3 cascade was involved in the FKBP5-regulating process. In the present study, FKBP5 was verified upregulated in cerebral I/R injury, related to the severity of ischemia and reperfusion injury. Additionally, our analyses revealed that FKBP5 regulates autophagy induced by OGD/R via the downstream AKT/FOXO3 signaling pathway. Our findings provide a novel biomarker for the early diagnosis of ischemic stroke and a potential strategy for treatment.

脑缺血性中风被认为是人类中枢神经系统中最严重的疾病之一。继发性缺血和再灌注（I / R）损伤增加了治疗难度。此外，I / R损伤的潜在分子调控机制仍不清楚。根据我们先前的临床研究，我们发现FK506结合蛋白5（FKBP5）在患有急性缺血性中风（AIS）的患者中明显上调，具有较高的诊断价值。FKBP5的水平与患者的神经功能障碍呈正相关。此外，小鼠短暂脑中动脉阻塞（tMCAO）模型被用于确认血浆中FKBP5表达可以反映其在脑组织中的相对水平。因此，我们假设FKBP5参与了脑I / R损伤的调节。体外。通过质粒稳定转染改变了FKBP5的表达水平。FKBP5表达的改变显着影响OGD / R损伤后的细胞活力和自噬。此外，AKT / FOXO3级联参与了FKBP5调节过程。在本研究中，FKBP5在脑I / R损伤中被上调，与缺血和再灌注损伤的严重程度有关。此外，我们的分析表明FKBP5调节OGD / R诱导的自噬通过下游AKT / FOXO3信号通路。我们的发现为缺血性中风的早期诊断提供了一种新颖的生物标志物，并为治疗提供了潜在的策略。