β-氨基丙腈饮水联合血管紧张素Ⅱ埋泵建立小鼠主动脉夹层模型

Establishment of a mouse model of aorta dissection induced by β-aminopropionitrile drinking combined with angiotensin Ⅱ infusion

目的应用β-氨基丙腈(β-aminopropionitrile,BAPN)饮水联合血管紧张素II(angiotensin II,Ang II)皮下埋泵建立小鼠主动脉夹层模型。方法 40只3周龄雄性C57Bl/6J小鼠随机分为两组,均每日给予0.1 g/(kg·bw)BAPN饮水,BAPN饮水后第28天给予皮下埋泵,BAPN饮水+生理盐水埋泵组持续泵入生理盐水,BAPN饮水+Ang II埋泵组持续泵入Ang II,每分钟1000 ng/(kg·bw)。采用小鼠无创血压测量计尾套法检测小鼠血压和心率。实验中死亡小鼠立即解剖,分离主动脉。埋泵72 h后,未死亡小鼠注射过量戊巴比妥钠处死,留取主动脉。苏木素-伊红染色显微镜下观察主动脉壁假腔形成情况。结果 BAPN饮水+Ang II埋泵组小鼠总的夹层发生率为95%,死亡率为24%(夹层动脉瘤破裂死亡),BAPN饮水+生理盐水埋泵组夹层发生率为5%,死亡率为0;镜下主动脉病理切片显示夹层主动脉有假腔形成。结论成功建立高主动脉夹层发生率的小鼠模型。

Objective To establish a mouse model of aorta dissection（ AD） by β-aminopropionitrile（ BAPN） in drinking water ＋ subcutaneously pumped angiotensin II（ Ang II） infusion. Methods Forty 3-week-old C57B1/6J male mice were randomly divided into two groups. All animals received 0. 1 g/kg/d BAPN in drinking water for 4 weeks. Then the BAPN drinking ＋ saline infusion group and BAPN drinking ＋ Ang II infusion group received continuous saline or Ang II（ 1,000 ng/kg/min） infusion,respectively,via subcutaneous osmotic minipump for 72 hour. The mice were restricted in a noninvasive computerized tail-cuff system and their arterial systolic blood pressure and heart rate were monitored. Autopsy was performed if a mouse died during the experiment. At the end of the experiment,mice were sacrificed by injection with an overdose of sodium pentobarbital and the aortas were harvested. The formation of aortic false lumen was observed by pa-thology using hematoxylin-eosin staining. Results The overall incidence of AD in the BAPN drinking administration ＋Ang II infusion group was 95%,whereas the incidence of AD in the BAPN drinking administration ＋ saline infusion group was only 5%. The mortality from dissecting aneurysm rupture was 24% in the BAPN drinking administration ＋ Ang II infusion group during the experiment. Pathological examination of the aortic cross-sections clearly showed the formation of blood-filled false lumens induced by Ang II. Conclusions A mouse model with high incidence of aortic dissection is successfully established.