Section of Vascular Surgery, University of Michigan, Cardiovascular Center, Ann Arbor, Michigan, USA.
J Surg Res. 2012 Dec;178(2):1038-45. doi: 10.1016/j.jss.2012.04.073. Epub 2012 May 18.
The objective of this study was to test a novel model of inducing abdominal aortic aneurysms (AAAs) in different mouse strains and genders.
Male and female C57BL/6 and B6129 mice (n = 5 per group) underwent periaortic dissection and porcine pancreatic elastase (30 μL) or inactivated elastase application (5 min) to the aorta. Aortic measurements were taken on days 0 and 14. Aortic samples were analyzed for histology and zymography for matrix metalloproteinase (MMP) activity. Comparison statistics were performed using unpaired t-test.
AAA phenotype (50% aortic increase) occurred in external elastase-treated males (100%) and females (90%). No control animals developed AAAs. The aortic diameter was larger in C57BL/6 and B6129 elastase-treated versus control males (P = 0.0028 and P < 0.0001, respectively) and females (P < 0.0001 and P = 0.0458, respectively). Histology verified phenotype via disrupted internal elastic laminae. Macrophage counts in elastase-treated animals were >6-fold higher than in controls (all groups significant). MMP9 activity was greater in elastase-treated males and females in C57BL/6 (P = 0.0031, P = 0.0004) and B6129 (P = 0.025, P = 0.2) mice; MMP2 activity was greater in C57BL/6 versus B6129 male elastase-treated mice.
This rodent model produced AAAs in both genders and strains of mice. This model is simple, has little variability, and occurs in the infrarenal aorta, substantiating the external elastase model for future studies.
本研究旨在测试一种诱导不同性别、不同品系小鼠腹主动脉瘤(AAA)的新型模型。
雄性和雌性 C57BL/6 及 B6129 小鼠(每组 n=5)行主动脉旁膜切开术,同时向主动脉内注射猪胰腺弹性蛋白酶(30μL)或非活性弹性蛋白酶(5min)。分别于第 0 天和第 14 天测量主动脉。分析主动脉组织学及明胶酶谱以检测基质金属蛋白酶(MMP)活性。采用独立样本 t 检验进行比较统计分析。
雄性和雌性外源性弹性蛋白酶处理组均发生 50%的AAA 表型(100%和 90%)。对照组无动物发生 AAA。与对照组相比,C57BL/6 和 B6129 弹性蛋白酶处理组雄性(P=0.0028 和 P<0.0001)和雌性(P<0.0001 和 P=0.0458)的主动脉直径更大。组织学证实弹性内弹力膜破裂导致了表型。与对照组相比,弹性蛋白酶处理组的巨噬细胞计数增加了 6 倍以上(所有组均有统计学差异)。MMP9 活性在 C57BL/6 弹性蛋白酶处理的雄性和雌性小鼠(P=0.0031,P=0.0004)和 B6129 小鼠(P=0.025,P=0.2)中均更高;MMP2 活性在 C57BL/6 雄性弹性酶处理组中高于 B6129 组。
该啮齿动物模型在不同性别和品系的小鼠中均能诱导 AAA。该模型操作简单,变异性小,发生于肾下主动脉,支持未来研究中采用外源性弹性蛋白酶模型。