提高缺血性脑卒中后M2型小胶质细胞比例可以促进神经功能恢复，但随着病情逐渐发展，M1/M2比例均衡的小胶质细胞主要转化为M1表型。因此，寻找抑制小胶质细胞极化为M2的病理因素并给予干预是促进脑缺血后神经功能重建的重要策略。脑缺血后三羧酸循环代谢中间产物琥珀酸大量堆积，胞浆内琥珀酸可以通过调节线粒体呼吸抑制小胶质细胞极化为M2型，而细胞外琥珀酸的功能并不清楚。新近有文献报道GPR91促进了细胞外琥珀酸介导的炎症反应，我们的预实验结果发现GPR91、CREB在M1/M2小胶质细胞中差异性表达。所以我们推测GPR91可能介导了细胞外琥珀酸抑制M2型小胶质细胞极化的病理过程，cAMP/CREB是GPR91抑制小胶质细胞极化为M2的重要通路。本项目拟通过神经功能评价、免疫组化、RNAi、流式细胞技术等方法，检测上述通路在脑缺血后小胶质细胞极化的作用，为临床治疗缺血性脑卒中提供新的干预靶点。

Improved M2 microglia proportion can promote neural functional recovery after cerebral ischemia stroke. With the development of illness, M1/M2 proportional microglia mainly polarize into M1 phenotype. Therefore intervention pathological factor which inhibits microglial polarizing into M2 phenotype is an important strategy for neural function reconstruction after cerebral ischemia. After ischemia, the Krebs cycle intermediate metabolism succinate accumulated, which in the cytoplasm can suppress microglia polarized into M2 type. However, the function of extracellular succinate is not clear. Recent literature reports that GPR91 participated in the extracellular succinate mediated inflammatory response, and our preliminary experiment found GPR91 and CREB were expression differences in M1 and M2 microglial. Hence, we speculated that GPR91 may mediated the function of inhibition M2 polarization by extracellular succinate through cAMP/CREB pathway. In order to prove our hypothesis, we use different molecular biological technique, such as such as functional evaluation, immunohistochemical, RNAi, flow cytometry to clarify the molecular mechanism of GPR91 and provide new intervention target for the treatment of cerebral ischemia stroke.