4种小鼠腹主动脉瘤模型的比较

4 abdominal aortic aneurysm mouse models

目的探讨和比较4种腹主动脉瘤小鼠模型特征,为腹主动脉瘤发病机制以及药物开发提供研究基础。方法 4种动物模型分别利用Apo E-/-基因敲除小鼠(n=8)皮下埋置血管紧张素Ⅱ微量渗透泵,持续28 d建立腹主动脉瘤模型;采用含0.01%苯并芘(Ba P)的高脂饲料喂养C57BL/6小鼠(n=10)同时皮下注射血管紧张素Ⅱ(Ba P模型)持续120 d,诱导腹主动脉瘤的形成;利用弹性蛋白酶(n=8)或氯化钙诱导C57BL/6小鼠(n=8)肾下主动脉瘤的发生,持续14 d,建立腹主动脉瘤模型。相同部位主动脉最大直径扩张1.5倍即判定主动脉瘤形成。结果与正常对照组比较,Apo E-/-模型小鼠腹主动脉直径明显增加(P<0.001),成瘤率为60%;Ba P模型小鼠腹主动脉直径增加,成瘤率为20%;弹性蛋白酶模型小鼠(P<0.001)、氯化钙模型小鼠(P<0.01)肾下腹主动脉直径增加,成瘤率分别为100%和75%。结论综合效果、时间、成本等因素,弹性蛋白酶诱导腹主动脉瘤的方法更加稳定可靠。

Objective To investigate and compare the characteristics of 4 mouse models and provide the basis for the pathogenesis and drug development for abdominal aortic aneurysm. Methods For mouse models were established： angiotensin H （Ang Ⅱ ） micro osmotic pump subcutaneously for 28 days on ApoE-/-knockout mice （n = 8）, high-fat diet containing benzopyrene （BaP） for subcutaneous injection of angiotensin Ⅱ （BaP model） for 120 days on C57BL/6 mice （n = 10）; elastase （n = 8） or calcium chloride used for 14 days on C57BL/6 mice （n = 8）. Until the aortic diameter was 1.5 times expanded in the same part to ensure the formation of aortic aneurysm. Results Compared with the control group, the diameter of the abdominal aorta in the ApoE-/- model mice was significantly increased （P 〈 0.001） with incidence rate of 60%. The abdominal aortic aneurysm formation rate was 20% in the BaP model. Both the diameters of the abdominal aorta in elastase model （P 〈 0.001） and the calcium chloride model （P 〈 0.01） were increased with abdominal aortic aneurysm incidence rate of 100% and 75%, respectively. Conclusion Inducing abdominal aortic aneurysm with elastase is more stable and reliable in terms of comprehensive effect, time and cost.