缺血性脑卒中是严重危害健康的常见病，AMP-活化蛋白激酶（AMPK）是调节细胞能量代谢的关键调控器，在脑缺血损伤与修复中发挥着重要作用，有望成为缺血性脑卒中治疗新靶点。申请人前期研究发现TAT转导的脑红蛋白（Ngb）在脑缺血中具有保护作用；而Ngb转基因小鼠脑组织AMPK活性明显减低，提示Ngb能在非缺血状态下抑制AMPK活性。那么，Ngb是否也能抑制脑缺血后的AMPK活性，进而调控脑缺血损伤与修复？明确这一重要科学问题将为缺血性脑卒中治疗研究提供新思路和新靶点。本项目立足上述前期研究，拟联合慢病毒转染、TAT蛋白质转导等技术，对AMPK基因敲除小鼠和Ngb转基因小鼠进行在体和离体研究，全面检测细胞代谢、细胞自噬、脑损伤与修复及AMPK信号通路等指标变化，明确AMPK在脑缺血损伤与修复中所发挥的作用及机制，阐明Ngb和TAT-Ngb融合蛋白对AMPK介导脑缺血损伤与修复的调控作用及机制。

Ischemic stroke is the most common subtype of cerebrovascular disease which has been the first leading cause of death in China since 2010. Acute ischemic stroke treatment is quite challenging for the evidence-based therapies are so limited. AMP-activated protein kinase (AMPK), which acts as a key metabolic regulator, would be an important potential target for stroke treatment and prevention. However, the role of AMPK in ischemic brain injury remains controversial. Our previous study indicates that neuroglobin (Ngb) transducted by TAT into brain has a protective effect on cerebral ischemia, and the overexpression of Ngb could significantly inhibit AMPK activation in the brain tissue of the Ngb transgenic mice. We hypothesis that Ngb might regulate brain injury and repair by AMPK during cerebral ischemia. The focal cerebral ischemic model of AMPK-knockout mice and Ngb transgenic mice in vivo and oxygen glucose deprivation (OGD) model in vitro will be used in this study. The cell energy metabolism, autophagy, brain damage and repair, the expressions of AMPK pathway cascades will be detected too. The aim of this study is to clarify the effect and mechanism of AMPK in the ischemic cerebral injury or repair and elucidate the regulatory role and mechanism of Ngb on AMPK.