A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

作者：Tanaka Akiko; Hasegawa Tomomi; Chen Zhi; Okita Yutaka; Okada Kenji^*

来源：Journal of Vascular Surgery, 2009, 50(6): 1423-1432.

DOI：10.1016/j.jvs.2009.08.062

Objective: 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.
Methods: 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 I-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 I 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.
Results: 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 mu m in group EC, 43.3% +/- 6.3% and 149.6 +/- 6.5 mu m in group E, and 10.9% +/- 4.2% and 152.9 +/- 7.2 mu m 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-1 beta 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.
Conclusion: 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. (J Vase Surg 2009;50:1423-32.)

• 出版日期2009-12