Tanaka Akiko, Hasegawa Tomomi, Chen Zhi, Okita Yutaka, Okada Kenji
Department of Surgery, Division of Cardiovascular Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
J Vasc Surg. 2009 Dec;50(6):1423-32. doi: 10.1016/j.jvs.2009.08.062.
An ideal animal model of abdominal aortic aneurysm (AAA) is of great importance for clarifying unknown complex mechanisms of the pathogenesis. We introduce a new, simple technique to create reliable AAAs that simulate human aneurysms.
Experimental models of AAAs were created in 71 rats by means of a 20-minute application of intraluminal elastase (30 U) and extraluminal calcium chloride (0.5M) in the 1-cm segment of infrarenal abdominal aorta (group EC, n = 26). A single application of elastase (group E, n = 24) or calcium chloride (group C, n = 21) was used as control. The treated aorta in each group was measured under physiologic conditions and harvested at 1 and 4 weeks. Successful AAA formation was defined as a dilation ratio >50%. Inflammatory response, elastolytic activity, and histology in the treated aorta were evaluated among the three groups.
The surgical procedure in each group was similarly completed for approximate 30 minutes and performed without any technical failure or operative death. At 4 weeks, the dilation ratio and wall thickness were 94.8% +/- 9.9% and 125.4 +/- 5.6 microm in group EC, 43.3% +/- 6.3% and 149.6 +/- 6.5 microm in group E, and 10.9% +/- 4.2% and 152.9 +/- 7.2 microm in group C. The success rate of AAA formation in group EC (92.7%) was significantly higher than that in group E (25.0%) and group C (0.0%). Less elastin content in the aortic wall was observed in group EC. At 1 week, tumor necrosis factor-alpha and interleukin-1beta messenger RNA (mRNA) expressions were significantly upregulated, and CD3+ and CD11b+ cells were significantly infiltrated into the treated aorta of group EC, compared with groups E or C. Gelatinolytic activities and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were also significantly activated in group EC.
The rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm similar to human AAAs. This model could be more useful to clarify AAA pathogenesis, mechanisms, and treatment interventions in experimental researches.
理想的腹主动脉瘤（AAA）动物模型对于阐明发病机制中未知的复杂机制至关重要。我们介绍一种新的、简单的技术来创建可靠的AAA模型，该模型可模拟人类动脉瘤。
通过在71只大鼠肾下腹主动脉1厘米节段腔内应用20分钟弹性蛋白酶（30 U）和腔外氯化钙（0.5M）创建AAA实验模型（EC组，n = 26）。单独应用弹性蛋白酶（E组，n = 24）或氯化钙（C组，n = 21）作为对照。在生理条件下测量每组处理后的主动脉，并在1周和4周时取材。AAA形成成功定义为扩张率>50%。评估三组处理后主动脉的炎症反应、弹性蛋白溶解活性和组织学情况。
每组手术过程均在约30分钟内顺利完成，无任何技术故障或手术死亡。4周时，EC组的扩张率和壁厚度分别为94.8%±9.9%和125.4±5.6微米，E组为43.3%±6.3%和149.6±6.5微米，C组为10.9%±4.2%和152.9±7.2微米。EC组AAA形成成功率（92.7%）显著高于E组（25.0%）和C组（0.0%）。EC组主动脉壁弹性蛋白含量较少。与E组或C组相比，1周时EC组处理后的主动脉中肿瘤坏死因子-α和白细胞介素-1β信使核糖核酸（mRNA）表达显著上调，CD3+和CD11b+细胞显著浸润。基质金属蛋白酶（MMP）-2和MMP-9的明胶溶解活性和mRNA表达在EC组也显著激活。
腔内注入弹性蛋白酶和腔外暴露氯化钙相结合的大鼠AAA模型操作简单，易于实施，高度可靠且可重复，能够创建类似于人类AAA的囊状动脉瘤。该模型在实验研究中对于阐明AAA发病机制、机制及治疗干预可能更有用。
