脑缺血-再灌注损伤时星形胶质细胞所起的作用尚未明确。我们前期体外实验发现在缺氧损伤时，星形胶质细胞外泌体miRNA-485表达显著增高，可抑制神经元p53通路并减轻神经元损伤程度。因此我们推测脑缺血-再灌注损伤时星形胶质细胞存在重要作用：其分泌的外泌体内miR-485表达增高，通过抑制神经元p53通路调控脑缺血-再灌注损伤。为明确这一假说，本项目拟首先在大鼠脑缺血模型中确认星形胶质细胞外泌体miR-485的调控作用；然后在体内外脑缺血模型中揭示星形胶质细胞外泌体miR-485通过抑制p53通路调控脑缺血-再灌注损伤并产生保护作用及具体机制；最后探索脑缺血时星形胶质细胞可通过激活HIF-1α而上调其外泌体内miR-485的表达水平。本课题有望明确星形胶质细胞外泌体miR-485通过抑制p53通路调控脑缺血-再灌注损伤的全新机制，为脑缺血-再灌注损伤的治疗提供新的思路及目标靶点。

The role and effect of astroglia in cerebral ischemia-reperfusion injury (I/R injury) has not been clarified. In the preliminary study, we found that the expression of miRNA-485 in astroglia exosome was significantly increased during hypoxia injury, which could inhibit p53 pathway and apoptosis in primary neuron, and alleviated neuronal damage in vitro. Therefore, we hypothesis that astroglia plays an important role in cerebral I/R injury: the up-regulation of miR-485 in the astroglia derived exosome could generate the protective effects against the cerebral I/R injury via inhibiting the p53 pathway in vivo. To demonstrate the hypothesis, this project intends to confirm the role of astroglia derived exosome miR-485 in distal MCA occlusion (dMCAO) model in rats firstly; then to reveal the mechanism on the protective effects of astroglia derived exosome miR-485 against cerebral I/R injury injury by inhibiting the p53 in Oxygen and Glucose Deprivation (OGD) model in vitro and cerebral ischemia model in vivo; finally to explore the cerebral I/R injury may activate HIF-1α pathway in astroglia and induce the miR-485 expression in the astroglia derived exosome. This research is expected to find the new mechanism of astroglia exosome miR-485 on the regulating the cerebral I/R injury by inhibiting the p53 pathway, and to provide new insights and targets for the treatment of cerebral I/R injury.