VEGF-A激活PI3K通路促进动脉瘤栓塞后瘤颈内皮化的作用及机制研究

Cerebral aneurysm rupture is the main cause of subarachnoid hemorrhage. Both fatality rate and disability rate are extremely high. Despite the minimally invasive and highly effective characteristics of intravascular interventional coil embolization, the recurrence of embolization is much higher than craniotomy clipping, which is the main defect of treatment. Previous studies showed that incomplete endothelialization was the main cause of recurrence of coiled aneurysm, so the development of endothelialization promotion drugs and materials has become the main solution of this problem. Our previous studies have demonstrated that EPCs can be mobilized by VEGF-A and promote endothelialization of the aneurysm neck, but the mechanism is not yet clear. In recent years, it has been found that the migration of endothelial cells around aneurysm neck after aneurysm embolization and the circulating EPCs adhesion are the main sources of aneurysm endothelialization, and the role of VEGF-A in promoting endothelialization may be related to the PI3K pathway. In this study, we will explore the role and mechanism of VEGF-A promoting aneurysm neck endothelialization after embolization through activating PI3K pathway. We plan to establish EPCs mobilization inhibited rat abdominal aortic aneurysm embolization model and use cell marker tracing technique and in vitro assay to illustrate the mechanism of PI3K pathway activated by VEGF-A to promote endothelial cells and EPCs. These result provide more information for the development of endothelialization promotion drugs and interventional materials.

脑动脉瘤破裂是蛛网膜下腔出血的主要原因，致死致残率高。血管内介入弹簧圈栓塞治疗虽然具有微创、高效的特点，然而其栓塞后复发远远高于开颅夹闭术，成为治疗的主要缺陷。已往研究表明: 动脉瘤颈内皮化不足是动脉瘤栓塞后远期复发的主要原因，故促内皮化治疗药物及材料的研发成为解决这一问题的重点。我们的前期研究已证明可通过VEGF-A动员内皮祖细胞并促进瘤颈内皮化，但其机制目前尚不清楚。近年来研究发现，动脉瘤栓塞后瘤颈周围内皮细胞迁移及循环血内皮祖细胞贴附为瘤颈内皮化的主要细胞来源，而VEGF-A的促内皮作用可能与PI3K通路相关。本研究将探究VEGF-A通过PI3K通路促进动脉瘤栓塞后瘤颈内皮化的作用，并利用内皮祖细胞动员抑制的大鼠腹主动脉瘤栓塞模型和细胞示踪技术，结合体外细胞试验，探究VEGF-A激活PI3K通路进而促进内皮细胞及内皮祖细胞的机制，为促内皮化药物和新型促内皮化介入材料的研发提供参考。

脑动脉瘤破裂是蛛网膜下腔出血的主要原因，致死致残率高。血管内介入弹簧圈栓塞治疗虽然具有微创、高效的特点，然而其栓塞后复发远远高于开颅夹闭术，成为治疗的主要缺陷。既往研究表明: 动脉瘤颈内皮化不足是动脉瘤栓塞后远期复发的主要原因，故促内皮化治疗药物及材料的研发成为解决这一问题的重点。本项目通过体内及体外试验证明，可通过VEGF-A及VEGF-A促进药物或小分子，通过PI3K通路动员内皮祖细胞并促进瘤颈内皮化。这一研究成果大程度地为动脉瘤栓塞后药物的使用提供了理论依据，也为新型介入器材的研发提供了生物学基础。