Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor.
Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor;
J Vis Exp. 2022 Feb 11(180). doi: 10.3791/63608.
Abdominal aortic aneurysm (AAA), although primarily asymptomatic, is potentially life-threatening as the rupture of AAA usually has a devastating outcome. Currently, there are several distinct experimental models of AAA, each emphasizing a different aspect in the pathogenesis of AAA. The elastase-induced AAA model is the second most used rodent AAA model. This model involves direct infusion or application of porcine pancreatic elastase (PPE) to the infrarenal segment of the aorta. Due to technical challenges, most elastase-induced AAA model nowadays is performed with the external application rather than an intraluminal infusion of PPE. The infiltration of elastase will cause degradation of elastic lamellae in the medial layers, resulting in the loss of aortic wall integrity and subsequent dilation of the abdominal aorta. However, one disadvantage of the elastase-induced AAA model is the inevitable variation of how the surgery is performed. Specifically, the surgical technique of isolating the infrarenal segment of the aorta, the material used for aorta wrapping and PPE incubation, the enzymatic activity of PPE, and the time duration of PPE application can all be important determinants that affect the eventual AAA formation rate and aneurysm diameter. Notably, the difference in these factors from different studies on AAA can lead to reproducibility issues. This article describes a detailed surgical process of the elastase-induced AAA model through direct application of PPE to the adventitia of the infrarenal abdominal aorta in the mouse. Following this procedure, a stable AAA formation rate of around 80% in male and female mice is achievable. The consistency and reproducibility of AAA studies using an elastase-induced AAA model can be significantly enhanced by establishing a standard surgical procedure.
腹主动脉瘤（AAA）虽然主要是无症状的，但却是潜在的致命性疾病，因为 AAA 的破裂通常会导致灾难性的后果。目前，有几种不同的 AAA 实验模型，每种模型都强调 AAA 发病机制的不同方面。弹性蛋白酶诱导的 AAA 模型是第二常用的啮齿动物 AAA 模型。该模型涉及将猪弹性蛋白酶（PPE）直接输注或应用于肾下主动脉段。由于技术挑战，现今大多数弹性蛋白酶诱导的 AAA 模型都是通过 PPE 的外部应用而不是腔内输注来进行的。弹性蛋白酶的渗透会导致中膜弹性板层的降解，导致主动脉壁完整性丧失，随后腹主动脉扩张。然而，弹性蛋白酶诱导的 AAA 模型的一个缺点是手术操作的不可避免的变化。具体来说，分离肾下主动脉段、用于包裹主动脉的材料和 PPE 孵育、PPE 的酶活性以及 PPE 应用的时间持续时间等手术技术都是影响最终 AAA 形成率和动脉瘤直径的重要决定因素。值得注意的是，这些因素在不同的 AAA 研究中的差异可能导致可重复性问题。本文描述了一种通过将 PPE 直接应用于肾下腹部主动脉外膜来诱导 AAA 的详细手术过程。按照此程序，雄性和雌性小鼠的稳定 AAA 形成率约为 80%。通过建立标准的手术程序，可以显著提高使用弹性蛋白酶诱导的 AAA 模型进行 AAA 研究的一致性和可重复性。
