苯并芘(Bap)联合血管紧张素Ⅱ(AngⅡ)微泵释放法建立实验性小鼠腹主动脉瘤模型

Establishment of Mice Experimental Abdominal Aortic Aneurysm(AAA) Models by Benzo[a]Pyrene(BaP) Intraperitoneal Injection with Ang Ⅱ Infusion

目的探讨苯并芘(Bap)腹腔注射联合血管紧张素Ⅱ(AngⅡ)皮下微泵释放法建立实验性小鼠腹主动脉瘤模型的可行性。方法 48只雄性C57BL/6J小鼠随机分为4组:对照组、低剂量4周组、低剂量6周组、高剂量6周组。各实验组小鼠经处理后,取腹主动脉瘤、观察其大体形态;切片行HE染色、Masson染色,进行统计学及组织学的评估;采用免疫组织化学法检测各组腹主动脉MMP-12表达水平。结果高剂量6周组小鼠腹主动脉瘤形成率(83.3%)较其他3组(50.0%、41.7%、0)显著升高(P<0.05),高剂量6周组平均血管周长与其他3组比较也显著增大(1607±225μm vs 1408±246μm、1394±230μm、935±109μm,P<0.05)。免疫组织化学法检测提示高剂量6周组小鼠腹主动脉壁MMP-12表达(0.62±0.11)较其他3组(0.51±0.10、0.48±0.09、0.11±0.04)显著增多(P<0.05)。结论高剂量血管紧张素:[0.90mg/(kg·d)]皮下微泵释放6周联合苯并芘(Bap)腹腔注射能够高效地建立腹主动脉瘤模型。

Objective To investigate a method of benzo[a]pyrene（BaP） intraperitoneal injection with Ang Ⅱ infusion using a osmotic pump for establishment of mice experimental abdominal aortic aneurysm models. Methods C57BL/6J mice（10 to 12 months old male） were divided into four groups. Mice in the control group received weekly intraperitoneal injection of medium-chain triglycerides. Mice in low dose 4 weeks group received daily AngⅡ infusion（0.72mg/kg） and weekly intraperitoneal BaP injection（10mg/kg, dissolved in medium-chain triglycerides）. Mice in low dose 6 weeks group received daily AngⅡ infusion（0.72mg/kg） and weekly intraperitoneal BaP injection. Mice in high dose 6 weeks group received daily AngⅡ infusion（0.90mg/kg） and weekly intraperitoneal BaP injection. At the end abdominal aortic were taken. Aortic tissues were subject to HE, Masson for evaluation of vascular wall structure, collagen. The immunochemistry staining for evaluation the expression of matrix metalloproteinase-12. Results Compared with the other three groups, the incidence of AAA in the high dose 6 weeks group were significantly inproved（83.3% vs 50.0%,41.7%,0, P〈0.05）.Average circumference of aortic rings increased（1607225μm vs 1408246μm,1394230μm,935109μm, P〈0.05）. Immunohistochemistry staining showed the expression of MMP-12 were increased compared with the other three groups （0.620.11 vs 0.510.10,0.480.09,0.110.04, P〈0.05）. Conclusion The mice experimental abdominal aortic aneurysm models can be efficiently established by benzo[a]pyrene（BaP） intraperitoneal injection with Ang Ⅱ infusion[0.90mg/（kgd）] for 6 weeks.