改良的覆膜支架治疗兔宽颈动脉瘤的实验研究

Endovascular treatment of intracranial wide-necked aneurysms ( neck >= 4mm or neck/body >= 1/2 ) is a challenge, and the rates of incomplete embolization and recurrence are respectively more than 40%. Considering the aneurysm itself is a kind of arterial wall deficiency disease, Willis covered stent as a new method was invented by our team for endovascular treatment of intracranial wide-necked aneurysms, which can reconstruct the arterial wall. However, there is a poor attachment and a delay of endothelialization ( >6 months ) in some cases since clinical application, which increases the risk of endoleak, and thrombosis, and in-stent stenosis, and even rebleeding. In this study, we will reduce metal coverage rate of the stent to enhanced its attachment, and increase permeability of the graft, and load the drug ( statins ) to regulate vascular endothelial cell, then hastened endothelialization ( <=3 months ), and promoted aneurysm healing. Improved covered stents with microporous PTFE or biodegradable electrospum nanofibers grafts were randomly implanted to the treatment for elastase-induced wide-necked aneurysms in rabbits, compared with studies for a long-term follow-up from radiology and pathology, to evaluate its feasibility and effectiveness, and the endothelialization process, and key factors influencing the endothelialization of covered stent in vivo.

颅内宽颈动脉瘤（瘤颈>=4mm或颈/体>1/2）一直以来都是血管内介入治疗的难题，不完全栓塞率和复发率超过40%。鉴于动脉瘤本身是一种母体血管管壁缺陷性疾病，我们课题组研制开发的Willis覆膜支架为颅内宽颈动脉瘤提供了新的治疗方法，能够解剖重建母体血管，但广泛应用临床以来部分病例存在支架整体贴壁性欠佳和支架段血管内皮化时间延迟（>6个月），增加了内漏、血栓和再狭窄甚至再出血的风险。本课题拟降低支架金属覆盖率改善支架的贴壁性，且增加膜的通透性和加载药物（他汀类药物）调控内皮祖细胞，加速内皮化进程（<=3个月），促进病变愈合。并通过随机植入多孔的PTFE膜和生物可降解静电纺纳米纤维膜的覆膜支架治疗改良的弹性蛋白酶制作的兔宽颈动脉瘤模型，从影像学和组织病理学长期随访进行对照，评价其可行性和有效性以及覆膜支架内皮化进程与其关键影响因素。

颅内宽颈动脉瘤一直以来是血管内介入治疗的难题，不完全栓塞率和复发率超过40%。本课题为进一步改善Willis覆膜支架整体贴壁性和支架段血管内皮化时间延迟等难题，通过降低支架金属覆盖率改善支架的贴壁性，且增加膜的通透性和加载药物（阿托伐他汀）调控内皮细胞，加速内皮化进程（<=3个月），促进病变愈合。通过实验随机植入不同浓度的载阿托伐他汀生物可降解静电纺纳米纤维膜的覆膜支架治疗改良的弹性蛋白酶制作的兔宽颈动脉瘤模型，达到了预期的目的。体内体外实验一致性表明加载浓度10mg/gPLC的阿伐他汀钙支架促进内皮化程度显著，同时内膜增生不显著，1个月左右体内完成内皮化，3-6个月血管通畅，管径无明显狭窄，内膜增生不显著。这个结果对于进一步探索颅脑可降解载药覆膜支架奠定了基础，提供了客观的实验数据，向临床应用转化迈出了坚实的一步。