VEGF/Nrf-2通路在内皮祖细胞归巢进而促进动脉瘤栓塞后瘤颈内皮化过程中的作用研究

Coil embolization is a safe, efficient and minimally invasive technique in intracranial aneurysm therapy. However, the long-term recurrence rate after embolization remains a major problem that needs to be addressed. Previous studies have shown that incomplete endothelialization in aneurysm neck is the main cause of long-term recurrence after embolization, and VEGF-induced endothelial progenitor cells(EPCs) mobilization and homing play crucial roles in aneurysm neck endothelialization after embolization. We have demonstrated that EPCs are involved in the process of aneurysm neck endothelialization. In addition, erythropoietin and statins could mobilize EPCs via VEGF elevation to enhance endothelialization of aneurysm neck. And we also found the activation of VEGF related Nrf-2 pathway could promote EPCs homing through inhibiting inflammation in aneurysm neck. In this study, we plan to utilize rabbit aneurysm coiling model and other experiments in vitro to verify the mechanism of VEGF/Nrf-2 pathway in mobilizing and promoting the homing of EPCs, thereby promoting aneurysm neck endothelialization. And thus provide more information and clues for EPCs promotion drugs development and theoretical basis of new pro-endothelialization interventional materials.

血管内介入弹簧圈栓塞颅内动脉瘤是一种安全、高效且微创的治疗技术。然而，栓塞后动脉瘤的远期复发率偏高是当前需要解决的主要问题。以往研究表明: 瘤颈内皮化的不完整是导致动脉瘤栓塞后复发的重要原因，而VEGF介导的内皮祖细胞动员和归巢为栓塞后动脉瘤颈内皮化提供了极大的帮助。我们已证明内皮祖细胞参与了动脉瘤栓塞后瘤颈内皮化的过程，且促红细胞生成素、他汀类药物可以通过VEGF动员内皮祖细胞，加强瘤颈内皮化。同时我们发现VEGF通过激活Nrf-2降低瘤颈炎性反应，并促进内皮祖细胞归巢。本研究中，我们利用基于兔颈动脉瘤栓塞模型的动物实验和体外细胞实验，验证VEGF/Nrf-2信号通路在调节促进瘤颈内皮化过程中的作用及其机制，并进一步阐明该通路的关键蛋白，进而为内皮祖细胞促进药物和介入材料的研发提供新的靶点。

血管内介入弹簧圈栓塞颅内动脉瘤是一种安全、高效且微创的治疗技术。然而，栓塞后动脉瘤的远期复发率偏高是当前需要解决的主要问题。以往研究表明: 瘤颈内皮化的不完整是导致动脉瘤栓塞后复发的重要原因，而VEGF介导的内皮祖细胞动员和归巢为栓塞后动脉瘤颈内皮化提供了极大的帮助。本项目通过体内及体外试验证明，VEGF/Nrf-2信号通路在调节促进瘤颈内皮化过程中的有着重要作用，多种药物和小分子均可通过这一通路动员内皮祖细胞，加强瘤颈内皮化。这一原理及机制相关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。