脑缺血缺氧损伤后有大量的星形胶质细胞增生，GLT1负责星形胶质细胞约90%的谷氨酸重吸收，对维持谷氨酸浓度至关重要，但其调控机制仍不清楚。我们前期研究表明Rheb1/mTOR通路调节神经系统的发育，胰岛素增加GLT1的表达，提示胰岛素/Rheb/mTOR可能参与GLT1的表达及其功能。我们还发现mTOR抑制剂rapamycin引起GLT1的表达增加，提示星型胶质细胞内可能存在从mTOR到AKT的负反馈通路。本项目将利用小鼠MCAO模型、分子生物学、细胞生物学等多种技术，研究：在OGD模型和大脑缺血缺氧损伤中，1.神经元、星形胶质细胞数量和形态变化；2.胰岛素/Akt /mTOR信号通路对星形胶质细胞的生长的影响及对GLT1表达调节；3.胰岛素/Akt/mTOR信号通路对神经功能恢复的调节作用。研究结果将推进理解缺血缺氧损伤病理生理机制，对研究CNS缺血缺氧损伤和学习记忆等具有理论指导作用。

A large number of astrocytes proliferate after cerebral ischemia anoxic injury.GLT1 is responsible for about 90% of glutamate reabsorption in astrocytes, which is crucial for maintaining glutamate concentration but the regulation mechanism is still not clear. Our previous studies showed that the Rheb1 / mTOR pathway regulates the development of the nervous system and insulin increases the expression of GLT1, which suggests that insulin / Rheb / mTOR may be involved in GLT1 expression and its function. We also found that mTOR inhibitor rapamycin caused an increase in GLT1 expression, suggesting that there may be a negative feedback pathway from mTOR to AKT in astrocytes. The project will use mouse MCAO model, molecular biology, cell biology and other technologies to study: In the OGD model and cerebral ischemia and hypoxia injury, 1. The morphological changes of neurons and astrocytes; 2. The regulation of insulin / Akt / mTOR signaling pathway on astrocytes growth and GLT1 expression; 3. The regulation of insulin / Akt / mTOR signaling pathway on neural function recovery. The results of the study will promote the understanding of the pathophysiological mechanism of hypoxic-ischemic insult and provide theoretical guidance for studying the hypoxic-ischemic injury and learning and memory of CNS.