PRAS40作为Akt的下游分子，同时可与mTOR复合物结合。在我们前期工作中已证实Akt和mTOR通路均与脑缺血-再灌注损伤有关。而PRAS40可直接与两条通路发生作用，因此推测其在脑缺血-再灌注损伤中起到重要作用。基于这个假设，本研究将在前期工作证实PRAS40过表达对脑缺血-再灌注损伤起到保护作用的基础上，首先观察PRAS40蛋白缺失后是否加重大鼠体内脑缺血-再灌注损伤；体外是否增加糖氧夺获（OGD）所致原代混合培养神经元的损伤；其次明确可能的作用机制（影响Akt及mTOR通路、氧自由基的清除、细胞凋亡）；最后，应用已构建的PRAS40慢病毒载体，使其在PRAS40蛋白缺失大鼠脑皮层及原代混合培养神经元中表达PRAS40，观察是否可抵消PRAS40蛋白缺失的影响，缩小脑梗死面积、减轻损伤。通过本研究，期望明确PRAS40蛋白在脑缺血-再灌注损伤中所起的作用及机制。

The proline-rich Akt substrate of 40 kDa(PRAS40) protein is not only a substrate of Akt, but also an important component of the mammalian target of rapamycin complex 1 (mTORC1), thus, PRAS40 serves as a linker between Akt and mTOR pathways. In our previous works, we have found that Akt and mTOR pathways are related with the brain ischemia and reperfusion injury and overexpress PRAS will contribute the protective effect against stroke. According to these findings, in this study we first plan to observe if the deletion of PRAS40 protein will aggravate the brain ischemia and reperfusion related injury in rats in vivo, and worsen the injury of primary mixed neuron culture by OGD in vivo. Secondly, we try to find the possibly mechanism how PRAS40 affect the brain ischemia and reperfusion related injury(through Akt/mTOR pathway, ROS, cell apoptosis). At last, we will use the lentiviral vector of PRAS0 constructed already, to overexpress PRAS40 both in mixed neuron culture and in cortex of the rat brain, to see if it will abolish the effect of PRAS40 protein deletion and attenuate the brain ischemia and reperfusion related injury. Through this study, we hope to understand the important role of PRAS40 protein in brain ischemia, and offer a potential therapy target for brain ischemia in clinic. PRAS40