内皮祖细胞种植可降解支架的构建及其促进犬颈内动脉夹层动脉瘤修复的实验研究

Intracranial dissection is one of the common reasons for subarachnoid hemorrhage and cerebral infarction with high morbidity and mortality. The mortality is as high as 35% in bleeding patients and 50-70% in re-bleeding patients. Intracranial dissections remain a therapeutic challenge both surgically and endovascularly. Previous studies in our team demonstrate that stenting is an effective technique. However, there are several defects for this technique, including delayed endothelialization, thrombosis, over-proliferation of intimal tissue, in-stent stenosis, and adverse effects for children and adolescents. A novel, more flexible, degradable, self-expandable low porosity stent will be designed at the nano-meter level with high-molecular material in this project, which is used for the treatment of intracranial dissections. The stent serves as 1) a flow-diverter to accelerate in-aneurismal thrombosis, 2) a carrier for "planting" endothelial progenitor cells (EPCs) on the dissection region, in order to accelerate neointima and endothelialization of the lesion, and 3) a absorbable implant after healing. The objective of this project is to explore the efficacy, safety and mechanism of endothelialization by in vitro and in vivo experiments, and to provide a novel method for the endovascular treatment of intracranial dissections.

颅内夹层动脉瘤是蛛网膜下腔出血和脑梗死的常见原因之一，致残、致死率高，首次出血死亡率达35％，再次出血死亡率高达50～70％。该病治疗相对困难，是困扰神经外科医师的难题。课题组前期的研究表明，支架植入是治疗夹层动脉瘤的有效方法，但目前该技术存在内皮化缓慢，血栓形成、以及支架在血管内长期存留可能引起血管内膜过度增生、血管狭窄、影响未成年人血管生长等缺陷。本项目拟应用高分子材料在纳米水平构建一种柔顺性较好的、可完全降解的自膨式低孔率支架，用于颅内夹层动脉瘤的治疗。其设计理念包括： (1）通过血流导向作用促进瘤内血栓形成；（2）作为载体发挥局部"内皮祖细胞接种"的作用，使EPC在局部分化、增殖，快速修复损伤内膜、覆盖支架；（3）在病变血管组织学愈合后降解。本项目通过一系列的体外测试和动物实验，探索该支架系统的可行性、安全性及其内皮化机制，为颅内夹层动脉瘤的治疗提供新思路，为临床应用奠定实验基础。

颅内夹层动脉瘤是蛛网膜下腔出血和脑梗死的常见原因之一，致残、致死率高，首次出血死亡率达35％，再次出血死亡率高达50～70％。该病治疗相对困难，是困扰神经外科医师的难题。课题组前期的研究表明，支架植入是治疗夹层动脉瘤的有效方法，但目前该技术存在内皮化缓慢，血栓形成、以及支架在血管内长期存留可能引起血管内膜过度增生、血管狭窄、影响未成年人血管生长等缺陷。本项目拟应用高分子材料在纳米水平构建一种柔顺性较好的、可完全降解的自膨式低孔率支架，用于颅内夹层动脉瘤的治疗。其设计理念包括： (1）通过血流导向作用促进瘤内血栓形成；（2）作为载体发挥局部"内皮祖细胞接种"的作用，使EPC在局部分化、增殖，快速修复损伤内膜、覆盖支架；（3）在病变血管组织学愈合后降解。本项目通过一系列的体外测试和动物实验，探索该支架系统的可行性、安全性及其内皮化机制，为颅内夹层动脉瘤的治疗提供新思路，为临床应用奠定实验基础。