β-氨基丙腈联合血管紧张素Ⅱ改良法建立小鼠主动脉夹层模型

doi:10.12300/j.issn.1674-5817.2020.200

摘要/Abstract

摘要： 目的探讨一种构建小鼠主动脉夹层模型的改良方法。方法 β-氨基丙腈（β-aminopropionitrile,BAPN）联合血管紧张素Ⅱ（angiotensinⅡ,Ang-Ⅱ）建立小鼠主动脉夹层模型。100只6周龄雄性C57BL/6J小鼠随机取20只作为对照组,另80只用于造模,其中单纯BAPN组40只和BAPN+ Ang-Ⅱ组40只。BAPN组小鼠给予0.1 g·kg^-1·d^-1 BAPN饮水;BAPN+Ang-Ⅱ组小鼠除给予BAPN 0.1g·kg^-1·d^-1饮水外,皮下注射Ang-Ⅱ（根据时间调整注射剂量：1~7 d Ang-Ⅱ 剂量为1.5 mg·kg^-1·d^-1,8~14 d Ang-Ⅱ为 0.75 mg·kg^-1·d^-1,15~16 d Ang-Ⅱ为 0.375 mg·kg^-1·d^-1）,BAPN组注射等体积生理盐水。药物干预16 d后取材。记录小鼠体质量及饮水量,实验进程中小鼠如有死亡立即解剖,分析死因。实验17 d,将未死亡的小鼠颈部脱臼处死,留取组织备用;HE染色判断主动脉夹层形成情况。结果 BAPN+ Ang-Ⅱ组及BAPN组分别与对照组相比,动物饮水量均减少、体质量增加趋势减慢（P<0.05）。对照组夹层发生率及死亡率均为0;BAPN组夹层发生率为7.5%,死亡率为2.5%,BAPN+Ang-Ⅱ组夹层发生率为80%,死亡率为30%。BAPN+Ang-Ⅱ组小鼠均死于调整Ang-Ⅱ剂量后1~3 d,83.3%小鼠死于注射药物后数分钟。结论给于C57BL/6J小鼠持续BANP饮水联合Ang-Ⅱ皮下注射成功构建主动脉夹层模型,具有周期短、模拟效果确切、死亡时间有一定规律、经济、稳定可重复等优点。

关键词: 主动脉夹层, β-氨基丙腈;, 血管紧张素Ⅱ, 小鼠

Abstract: Objective To explore an improved method for constructing a mouse model of aortic dissection (AD). Methods AD was induced by the simultaneous administration of β-aminopropionitrile (BAPN) with angiotensin Ⅱ (Ang-Ⅱ) for 16 days in mice. One hundred 6-week-old male C57B1/6J mice were randomly divided into BAPN (BAPN 0.1 g•kg^-1•d^-1 + 0.9% saline), BAPN+Ang-Ⅱ (BAPN 0.1 g•kg^-1•d^-1 + Ang-Ⅱ), and control groups. BAPN (0.1 g•kg^-1•d^-1), freshly prepared and dissolved in drinking water, was administered to all mice in the BAPN and BAPN + Ang-Ⅱ groups for 16 days. Mice in the BAPN+Ang-Ⅱ group were treated with an additional subcutaneous injection of Ang-Ⅱ for 16 days. The concentration of Ang-Ⅱ was halved from 1.5 mg•kg-1•d-1 every week until it was set at 0.375 mg•kg^-1•d^-1 on day 15, and then maintained. The daily water intake and body weight were recorded from the beginning until the end of the study. If a mouse died during the experiment, an autopsy was performed to analyze the cause of death. On day 17, the mice were sacrificed, and each aorta was harvested. The formation of the aortic false lumen was observed pathologically using hematoxylin and eosin (HE) staining. Results Compared with the control group, the amount of water consumed and body weight in the BAPN+Ang-Ⅱ and BAPN groups were significantly reduced (P < 0.05). In the control group, the incidence of dissection and mortality was 0.0%. In the BAPN group, the incidence of AD and the mortality was 7.5% and 2.5%, respectively. In the BAPN+Ang-Ⅱ group, the incidence of AD and the mortality was 80.0% and 30.0%, respectively. Interestingly, the deaths in the BAPN+Ang-Ⅱ group occurred frequently at 1-3 days after dose adjustment, and 83.3% of the mice died a few minutes after the operation. Conclusion This modified method for constructing an AD mouse model induced by BAPN drinking combined with Ang-Ⅱ subcutaneous injection was replicable, regular, effective, cheap, and quick.

Key words: Aortic dissection, Beta-aminopropionitrile, Angiotensin Ⅱ, Mice

中图分类号:

Q95-33

程玲霞, 陈琳, 杨帆, 刘英, 陈睦虎, 胡迎春, 宋其泰, 钟武. β-氨基丙腈联合血管紧张素Ⅱ改良法建立小鼠主动脉夹层模型[J]. 实验动物与比较医学, 2021, 41(4): 321-326.

CHENG Lingxia, CHEN Lin, YANG Fan, LIU Ying, CHEN Muhu, HU Yingchun, SONG Qitai, ZHONG Wu. A Modified Method of β-Aminopropionitrile Combined with Angiotensin Ⅱ to Establish an Aortic Dissection Model in Mice[J]. Laboratory Animal and Comparative Medicine, 2021, 41(4): 321-326.

图/表 4

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