可吸收血流导向支架治疗兔囊状宽颈动脉瘤及对正常分支血管的影响

Embolization of wide-necked saccular aneurysms by coils remains challenging, with high recurrence rates in angiographies and embolism event. A remarkable curing rate (95%) has been achieved in the treatment of intracranial intractable aneurysms by using flow-diverting devices in the past 5 years, and it changes the sales philosophy of treating intracranial aneurysm from dome of aneurysm embolization to parent artery reconstruction. However, this new device may lead to stenosis or occlusion of side branches or perforators once covered with dense metal mesh in treating intracranial aneurysms. The metal flow diversion stents with at least 35% metal coverage can cure aneurysms in early studies, but the device with metal coverage more than 40% can cause severe neointima coverage at ostium of branch. In this study, we will use biodegradable flow diverting stent (Polyglycolic Acid, Polylactic acid- Polyglycolic acid) with 35%- 40% struts coverage to inspect aneurysm occlusion and normal abdominal aorta and branch arteries after implanted. By observing the effects on aneurysm and normal abdomen aorta branch artery after the biodegradable flow diverting stent implanted at different time points in 3 months follow up, we will look up the biodegradable regularity of this new device. Then we will study the long term (6 to 12 months) effects of biodegradable flow diverting stent on aneurysm and normal abdomen aorta branch artery by angiographic, hemodynamic and pathologic methods. We anticipate the real reconstruction of artery in biology after the thrombus induced by biodegradable flow diverting stent, and organization of thrombus in aneurysm after the struts of stent degradation.

颅内宽颈动脉瘤栓塞后复发和梗塞事件是目前介入治疗面临的难题之一，近5年出现的金属血流导向支架使动脉瘤介入治疗的理念由瘤体栓塞变为血管重建，其治愈率高达95%，但这种高金属覆盖率（30%以上）支架在治愈动脉瘤的同时也引起正常血管及分支开口内膜严重增生。研究表明血流导向支架金属覆盖率只有达到35%才能完全预测动脉瘤愈合，而金属覆盖率超过40%则易引起正常分支开口内膜过度增生。本课题将研究可吸收材料制作的血流导向支架（聚乙醇酸，聚左旋乳酸-乙醇酸，覆盖率35-40%）对动脉瘤的治疗效果和对分支的影响。通过短期（3个月内）动物实验，观察可吸收材料在血管内降解规律及在不同时间点对动脉瘤的治疗作用和对正常分支的影响。再对该支架治疗动脉瘤效果和对分支影响进行长期（6-12个月）影像学、血流动力学和病理学研究。相信随着可吸收血流导向支架诱导动脉瘤内血栓和机化，可吸收成分降解，将在生物意义上实现血管修复。

近年来使用血流导向金属支架（MFD）治疗颅内宽颈动脉瘤发展迅速，但过高的金属覆盖率长期对血管壁的炎性刺激仍会导致载瘤动脉狭窄及穿支血管的闭塞。本研究观察了使用可吸收材料（聚乙醇酸，PGA；聚乳酸-乙醇酸，PGLA）制作的血流导向支架(PGA-FD和PGLA-FD)对兔动脉瘤的治疗效果和对分支的影响。①、设计可吸收支架治疗动脉瘤的理想参数，使其有效网丝覆盖率达40%-50%，而可降解材料降解后其金属覆盖率降低至15%-20%。改进对实验所用的弹性蛋白酶诱导的兔动脉瘤模型制作方法。②、观察了可吸收血流导向支架对兔动脉瘤和分支血管的短期（＜3个月）影响。实验显示：PGA-FD导致的动脉瘤闭塞分级明显高于MFD（P<0.01），两组均未见所覆盖的分支血管闭塞。可吸收材料术后6周在新生内膜内部分降解，3个月时完全吸收，原可吸收网丝处新生内膜由平滑肌细胞填充。新生内膜主要由平滑肌细胞和胶原纤维组成，新生内膜表面可见血管内皮细胞。③、观察了可吸收血流导向支架对兔动脉瘤和分支血管的中长期（6-12个月）影响。结果显示PGA和PGLA两种支架导致的动脉瘤闭塞分级无统计学差异（P>0.05），PGLA导致的动脉瘤闭塞分级明显高于MFD（P<0.05）。这些支架导致的新生内膜厚度无统计学差异（P>0.05），支架所覆盖的血管无明显狭窄，分支无闭塞。支架所引起的新生内膜成分与短期效果类似。④、对支架置入前后动脉瘤内的血流动力学分析，并通过fisher判别分析，得出预测动脉瘤闭合公式。⑤、对金属血流导向支架两端形态分析研究表明：无论直形开口或喇叭形开口，均可见少量金属网丝不能贴合血管壁或刺破血管，但未见壁内血栓或血管外出血。喇叭口总的网丝贴壁不良数与直口比较无统计学差异（P>0.05）。随着可吸收血流导向支架诱导动脉瘤内血栓和机化，可吸收成分降解，既能达到治疗动脉瘤的效果，又能避免内膜过度增生、分支血管闭塞等严重并发症。有关课题内容已发表文章2篇，录用2篇，投稿修回1篇，在写1篇，申请专利3项。