Yue Jianing, Yin Li, Shen Jian, Liu Zhenjie
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ann Vasc Surg. 2020 Aug;67:474-481. doi: 10.1016/j.avsg.2020.03.002. Epub 2020 Mar 12.
The perfused elastase AAA model and subcutaneous Angiotensin II infusion AAA model are widely used murine AAA models. We modified these two current models and developed a new murine model to study aneurysm formation and rupture.
The murine abdominal aorta was treated with elastase. Angiotensin II was infused at a dose of 1,000 ng/kg/min via an osmotic pump placed subcutaneously. A saline osmotic pump was used as the control. The aortas were harvested from the mice 4 weeks later, or earlier if mice died. The abdominal aorta was inspected using ultrasound and microscopy for aneurysm formation and/or signs of rupture. The aneurysm outcome was measured using aortic expansion and proinflammatory cytokine expression. It was also compared with the established conventional elastase perfusion and angiotensin II infusion abdominal aortic aneurysm models.
By day 28 after surgery, all abdominal aortas of mice treated in the modified group had dilated and progressed to abdominal aortic aneurysms with 60% ruptured aneurysms, whereas none of the control aortas treated with saline became aneurysmal. In mice treated with elastase solution alone, 100% developed aneurysms and only one had a ruptured aneurysm. In mice given angiotensin II infusion alone, 37.5% developed aneurysms and none had a ruptured aneurysm. Histological examination of the modified murine abdominal aortic aneurysm rupture model was identical to that observed in the conventional elastase model. Quantitative polymerase chain reaction analysis revealed similarly increased levels of proinflammatory cytokines.
We modified two current murine abdominal aortic aneurysm models to develop a murine abdominal aortic aneurysm model with consistent aneurysm formation and high rupture incidence, which can be used for studying abdominal aortic aneurysm rupture and treatment.
灌注弹性蛋白酶腹主动脉瘤模型和皮下输注血管紧张素II腹主动脉瘤模型是广泛使用的小鼠腹主动脉瘤模型。我们对这两种现有模型进行了改良,开发出一种新的小鼠模型来研究动脉瘤的形成和破裂。
用弹性蛋白酶处理小鼠腹主动脉。通过皮下植入的渗透泵以1000 ng/kg/分钟的剂量输注血管紧张素II。使用盐水渗透泵作为对照。4周后从小鼠体内取出主动脉,若小鼠死亡则提前取出。使用超声和显微镜检查腹主动脉有无动脉瘤形成和/或破裂迹象。通过主动脉扩张和促炎细胞因子表达来测量动脉瘤结果。还将其与已建立的传统弹性蛋白酶灌注和血管紧张素II输注腹主动脉瘤模型进行比较。
术后第28天,改良组处理的小鼠所有腹主动脉均扩张并发展为腹主动脉瘤,其中60%的动脉瘤破裂,而用盐水处理的对照主动脉均未形成动脉瘤。仅用弹性蛋白酶溶液处理的小鼠中,100%形成动脉瘤,只有1例动脉瘤破裂。仅给予血管紧张素II输注的小鼠中,37.5%形成动脉瘤,无一例动脉瘤破裂。改良小鼠腹主动脉瘤破裂模型的组织学检查与传统弹性蛋白酶模型观察到的结果相同。定量聚合酶链反应分析显示促炎细胞因子水平同样升高。
我们改良了两种现有的小鼠腹主动脉瘤模型,开发出一种具有一致动脉瘤形成和高破裂发生率的小鼠腹主动脉瘤模型,可用于研究腹主动脉瘤破裂及治疗。