脑缺血后小胶质细胞TLRs与内质网应激信号通路的交互作用促进炎症因子释放介导神经损伤的研究

Cerebral ischemia reperfusion injury (CIRI) has been recognized as a common pathophysiological process during ischemic stroke. Recent studies have shown that inflammatory immune response plays an important role in CIRI. However, the activation of microglia induced by TLR2 and the following release of inflammatory factors becomes the key mechanisms of neuronal damage after CIRI. Our previous studies have confirmed that expression of TLR2 was increased in microglia after CIRI, which promoted inflammatory cytokines IL17 release, finally led to neuronal apoptosis, another study also reported that ERS activation in microglia can regulate the expression of TLR2, meanwhile TLR2 deficiency increased ERS, which explicited positive feedback, but there is no report about the regulation between TLR2 and ERS in activated microglia after CIRI, and how they regulated neuronal damage remained unknown. This project is based on previous studies, we will administrated in vivo and in vitro experiments to further clarify the role of microglia in ERS and TLR2 in CIRI, the overexpression and knockdown technology will be used, CHIP and EMSA technology are used to clarify the molecular regulation mechanism between ERS and TLR2 in CIRI and detect the ERS-TLR2 interaction in the excessive activation of microglia in CIRI, which will provide new ideas and look for new targets for the treatment of stroke.

脑缺血再灌注损伤(CIRI)是缺血性脑卒中一个常见的病理生理过程，近年来的研究结果显示炎症免疫反应是CIRI中的重要环节，而TLR2诱导的小胶质细胞过度活化，释放炎症因子是CIRI神经细胞损伤的关键机制之一。我们前期研究证实CIRI后小胶质细胞TLR2表达上调，促进下游炎症因子IL17的表达并且诱导神经元凋亡，另有研究报道显示小胶质细胞ERS激活后能够调控TLR2表达，并且TLR2能够正反馈促进ERS及小胶质细胞的激活，但其在CIRI激活小胶质细胞调控神经元损伤中未见报道。本项目拟在前期研究基础上，通过体内、体外实验进一步明确小胶质细胞ERS、TLR2在CIRI中的作用，采用过表达和敲低、CHIP及EMSA等技术探讨脑缺血后ERS、TLR2在CIRI中的相互间调控关系，阐明脑卒中后ERS-TLR2交互作用在小胶质细胞过度活化介导的CIRI中的分子调控机制，为脑卒中治疗性提供新思路和靶点。

脑缺血再灌注损伤(CIRI)是缺血性脑卒中一个常见的病理生理过程，近年来的研究结果显示炎症免疫反应是CIRI中的重要环节，而TLR2诱导的小胶质细胞过度活化，释放炎症因子是CIRI神经细胞损伤的关键机制之一。我们前期研究证实CIRI后小胶质细胞TLR2表达上调，促进下游炎症因子IL17的表达并且诱导神经元凋亡，另有研究报道显示小胶质细胞ERS激活后能够调控TLR2表达，并且TLR2能够正反馈促进ERS及小胶质细胞的激活，但其在CIRI激活小胶质细胞调控神经元损伤中未见报道。本项目拟在前期研究基础上，通过体内、体外实验进一步明确小胶质细胞ERS、TLR2在CIRI中的作用，采用过表达和敲低、CHIP及EMSA等技术探讨脑缺血后ERS、TLR2在CIRI中的相互间调控关系，阐明脑卒中后ERS-TLR2交互作用在小胶质细胞过度活化介导的CIRI中的分子调控机制，为脑卒中治疗性提供新思路和靶点。