颈动脉分叉部动脉瘤模型形态学、血流动力学和组织病理学研究

Carotid artery bifurcation aneurysm model: a morphological, hemodynamic and histopathological study

目的建立犬动物模型,研究特定血流动力学变化及动脉壁退化是否会导致动脉瘤发生发展。方法建立18只犬颈总动脉(CCA)新分叉模型,随机分组为弹力蛋白酶处理组(EBG,n=9)和分叉模型对照组(CBG,n=9);同时设弹力蛋白酶处理直段CCA对照组(ESG,n=3)。术后即刻,术后12周、24周分别行血管造影及血流动力学分析,术后12周和24周行组织病理学分析。结果血管造影显示EBG组5只犬模型CCA分叉顶部出现新生动脉瘤形成,瘤体平均直径(3.2±0.4)mm,CBG组和ESG组均未观察到新生动脉瘤形成;EBG组新生动脉瘤在随访期间未见破裂。组织学分析显示EBG组内层弹力膜不连续、弹力纤维断裂、肌层变薄、平滑肌细胞减少,炎性细胞(巨噬细胞)浸润及MMP-2、MMP-9表达增多(与CBG组和ESG组对比,P<0.001)。血流动力学分析显示EBG组分叉顶部壁面切应力减低、血流速度减慢、相对压力和总压力最高,动脉壁重塑后均恢复正常。结论本实验表明动脉壁退化和动脉分叉处血流动力学作用可导致犬模型新生动脉瘤形成。

Objective To establish carotid artery bifurcation aneurysm in canine, and to clarify whether specific hemodynamic insult in combination with arterial wall degeneration will lead to the occurrence and development of aneurysms. Methods New bifurcation aneurysm model of common carotid artery （CCA） was successfully established in 18 dogs, which were randomly divided into the elastase-treated bifurcation group （EBG,n=9） and the control bifurcation group （CBG,n=9）. Three dogs were treated with elastase insult to both straight sections of CCA and were used as elastase-treated straight section group （ESG,n =3）. Angiographic and hemodynamic analysis was conducted immediately after the operation, as well as 12 and 24 weeks after the operation. Histopathological examination was performed 12 and 24 weeks after the operation. Results Angiography showed that new aneurysm （mean diameter 3.2±0.4 ram） was formed at the apex of CCA bifurcation in 5 dog models of EBG group, while no new aneurysm was observed in both CBG and ESG groups. In EBG group, no rupture of the new aneurysm occurred during the follow-up period. Histological analysis revealed that in EBG group the inner elastic lamina was discontinued, the elastic fiber was disrupted, the muscle layer became thinned, the smooth muscle cells were reduced, and the inflammatory cell （maerophage） infiltration as well as the expressions of MMP-2 and MMP-9 were increased; these changes were statistically significant when compared with those in CBG group and ESG group （P〈0.001）. Postoperative hemodynamic analysis indicated that in EBG group the wall shear stress at the apex of CCA bifurcation was reduced, the blood flow velocity was decreased, with the relative and total pressure being the highest; all the above changes returned to normal after arterial wall remodeling. Conclusion The results of this study indicate that the arterial wall degeneration and the hemodynamic effect at the apex of CCA bifurcation can lead to new aneurysm formation in canine model.