远隔预处理调控TRAIL-DcR1/DcR2诱导脑保护的机制研究

远隔预处理（RPC）可以减少缺血性脑损伤的梗死面积、促进神经功能恢复，但其诱导脑保护的作用机制尚未阐明。本课题组前期研究发现抗凋亡是其发挥脑保护作用的重要机制，RPC能够抑制脑缺血后外源性凋亡通路激活、下调TRAIL死亡受体表达及上调TRAIL诱饵受体表达，推测TRAIL及其诱饵受体(DcR1和DcR2）很有可能是RPC诱导缺血脑保护的关键调控分子之一。本课题拟进一步研究RPC诱导缺血脑保护过程中TRAIL死亡受体和诱饵受体的在表达水平、细胞定位上有何变化？通过过表达和shRNA干扰技术验证TRAIL及其诱饵受体参与预处理诱导神经保护的作用，通过干预TRAIL受体蛋白表达的方法在细胞水平探讨诱饵受体通过何种途径介导RPC的保护作用，以明确RPC诱导缺血脑保护作用的关键调控分子，为RPC的临床转化提供理论依据，并为缺血性脑损伤的药物研发提供新的可能的靶点。

Remote preconditioning (RPC) ameliorates brain damage, neuronal apoptosis and neurological dysfunction after ischemic cerebral stroke (ICS).However its molecular mechanism isn’t yet definitive. The extrinsic apoptosis pathway was induced by TRAIL bound to death receptors, but it was inhibited by TRAIL bound to decoy receptors. In our previous study, we found that RPC could inhibite the extrinsic apoptosis pathway action, down-regulate expression of death receptors, and up-regulate expression of decoy receptors. Therefore, we hypothesis that TRAIL and TRAIL-receptors maybe plays an important role in RPC neuroprotective mechanism. In order to verify our hypothesis, we will investigate the expression profile changes of death receptors and decoy receptors after ICS. Meanwhile, intervention expression of TRAIL-receptors in-vitro will be employed to investigate molecular mechanism of decoy receptors induced neural biological mechanism that RPC induced ischemic cerebral protection and to provide evidence for its clinical application, we also hope to find new pharmaceutic therapy target of endogenous cerebral protection through this project.