SUMO修饰SIRT3/TFAM信号轴介导拟黑多刺蚁减轻脑缺血再灌注内皮损伤的机制研究

脑血管内皮功能障碍是导致脑缺血再灌注（CI/R）损伤的原因之一，其中线粒体呼吸链功能障碍损害内皮功能，导致脑缺血恢复期血管新生的不足，影响血运重建。我们前期结果表明沉默信息调节因子3（SIRT3）参与拟黑多刺蚁活性组分（AFPR）拮抗CI/R损伤机制，但机制未明。我们预实验发现，AFPR能减少SIRT3-SUMO化修饰，激活SIRT3-TFAM轴调控线粒体呼吸链功能。因此，本项目提出AFPR通过激活“PIAS1-SIRT3-TFAM”轴改善线粒体呼吸链功能，进而减轻CI/R所致内皮损伤的假说，并进一步探讨：①AFPR对CI/R所致内皮损伤的保护作用；②“PIAS1-SIRT3-TFAM”信号轴调控脑微血管内皮线粒体呼吸链功能在AFPR发挥抗CI/R损伤作用的相关机制。充实线粒体功能在脑缺血内皮损伤中的机制，为拟黑多刺蚁抗进行脑缺血药物开发提供理论依据。

As one of the main reasons for cerebral ischemia reperfusion (CI/R) injury, cerebral endothelium dysfunction, especially mitochondrial electron transport chain (ETC) dysfunction, may reduce cerebral angiogenesis in late-stage of stroke. Our previous studies indicated active fraction from Polyrhachis Vicina Roger (AFPR) showed protective effects on CI/R injury through regulation of mitochondrial function via SIRT3, but the mechanism remained unclear. Further studies revealed AFPR might reduce SUMO modification of SIRT3, and promote mitochondrial ETC function through up regulation of SIRT3-TFAM axis. Therefore, we hypothesize that AFPR protects against CI/R injury by promoting mitochondrial ETC function in cerebral microvascular endothelium via up-regulating PIAS1-SIRT3-TFAM axis. Actions and mechanisms of AFPR need to be clarified in the following study: ① Protective effect of AFPR against endothelium injury after CI/R. ②Effects of AFPR in regulating mitochondria ETC function after CI/R though “PIAS1-SIRT3-TFAM” axis. Eventually, the study may help enrich research on regulation of mitochondrial ETC function in CI/R induced microvascular endothelium injury, and accelerate future applications of AFPR.