甲基巴多索龙在 BAPN 诱导小鼠主动脉夹层模型中的作用评估

doi:10.3969/j.issn.1006-7795.2026.01.018

首都医科大学学报

甲基巴多索龙在 BAPN 诱导小鼠主动脉夹层模型中的作用评估

刘周^1,2,3, 梁嘉俊^1,2, 刘瑞飞^1,2, 姜文剑^1,2,3, 张宏家^1,2, 赵远斐^1,3*

1.首都医科大学附属北京安贞医院北京市心肺血管病疾病研究所，北京 100029；2.首都医科大学附属北京安贞医院心脏外科，北京 100029；3.首都医科大学基础—临床联合实验室，北京 100029

收稿日期:2025-09-05 修回日期:2025-10-29 出版日期:2026-02-21 发布日期:2026-01-20
通讯作者: 赵远斐 E-mail:yfzhao89@outlook.com
基金资助:
北京市自然科学基金项目 (24G10071），北京市科技新星计划（20220484151），安贞医院杰青优青培养计划（AZ2023-YQ-04），国家自然科学基金-优秀青年科学基金项目（82422007），国家自然科学基金（82241205），北京市自然科学基金-杰出青年科学基金项目（JQ24038）。

Evaluation of the role of bardoxolone methyl in BAPN-induced mouse aortic dissection mode

lLiu Zhou^1,2,3， Liang Jiajun^1,2， Liu Ruifei^1,2， Jiang Wenjian^1,2,3， Zhang Hongjia^1,2， Zhao Yuanfei^1,3*

1.Beijing Anzhen Hospital, Capital Medical University Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China；2.Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China；3.Laboratory for Clinical Medicine, Capital Medical University, Beijing 100029, China

Received:2025-09-05 Revised:2025-10-29 Online:2026-02-21 Published:2026-01-20
Supported by:
This study was supported by Beijing Natural Science Foundation (24G10071）,Beijing Nova Program（20220484151）,Outstanding Young Talents Cultivation Program for Jieqing & Youqing of Beijing Anzhen Hospital, Capital Medical University（AZ2023-YQ-04）, Excellent Young Scientists Fund of the National Natural Science Foundation of China（82422007）, National Natural Science Foundation of China（82241205） and Distinguished Young Scientists Fund of Beijing Natural Science Foundation (JQ24038）.

摘要/Abstract

摘要： 目的本研究旨在进一步探究甲基巴多索龙（bardoxolone methyl, BM）在小鼠主动脉夹层（aortic dissection，AD）模型中的治疗效果。方法研究采用3周龄雄性C57BL/6J小鼠，通过喂养含0.4%(质量分数)的β-氨基丙腈（β-aminopropionitrile,BAPN）饲料构建AD模型。采用数字表法随机将小鼠分为对照组、BAPN对照组和BAPN+BM组。BAPN+BM组给予每日1.25 mg/kg剂量的BM腹腔注射干预4周，对照组注射等量溶剂。实验期间记录小鼠生存情况并行超声检测，实验结束后行主动脉解剖及病理染色评估主动脉病变情况。结果在28 d实验周期内，BAPN对照组与BAPN+BM组小鼠均出现较高病死率（72.7% vs 63.6%，P>0.05）。尽管BM干预可以延缓死亡时间，但并未显著改善生存率。超声结果显示，两组小鼠胸主动脉均出现不同程度扩张，差异无统计学意义。解剖及病理学分析发现，BM未能显著降低主动脉夹层发生率，也未能改善中膜结构破坏、胶原沉积及弹性纤维断裂等病理学损伤。结论每日1.25 mg/kg剂量下BM在BAPN诱导的小鼠AD模型中未表现出显著保护作用，表明了腹主动脉瘤（abdominal aortic aneurysm，AAA）与AD动物模型在同一剂量BM药物反应上的差异性，为不同类型主动脉疾病的个性化干预策略提供了参考。

关键词: 主动脉夹层, 腹主动脉瘤, 甲基巴多索龙, 动物模型, 炎症, 氧化应激

Abstract: Objective Previous studies have shown a protective effect of bardoxolone methyl (BM) in an abdominal aortic aneurysm (AAA) model, and this study aims to further explore its therapeutic effect in aortic dissection (AD) model.Methods A 3-week-old male C57BL/6J mouse was fed a β-aminopropionitrile (BAPN) diet containing 0.4% mass fraction to construct an AD model. The mice were randomly divided into control group, BAPN control group and BAPN+BM group. The BAPN+BM group was given a dose of 1.25 mg/kg per day intraperitoneal injection for 4 weeks, and the control group was injected with the same amount of solvent. During the experiment, the survival of mice was recorded and ultrasound detection was conducted, and aortic anatomy and pathological staining were performed to evaluate the aortic lesion after the experiment.Results During the 28-day experimental period, both the BAPN control group and the BAPN+BM group had a higher mortality rate (72.7% vs 63.6%, P>0.05). Although BM interventions can delay the time to death, they do not significantly improve survival. Ultrasound results showed that the thoracic aorta of the mice in both groups had different degrees of dilation, and the difference was not significant. Anatomical and pathological analysis showed that BM failed to significantly reduce the incidence of aortic dissection, nor did it improve pathological injuries such as media structure damage, collagen deposition, and elastic fiber rupture.Conclusion BM at 1.25 mg/kg per day did not show significant protective effect in BAPN-induced mouse AD models, indicating the differences between AAA and AD animal models in the same dose of BM drug response, which provided a reference for personalized intervention strategies for different types of aortic diseases.

Key words: aortic dissection, abdominal aortic aneurysm, bardoxolone methyl, animal model, inflammation, oxidative stress

中图分类号:

R654.3

刘周, 梁嘉俊, 刘瑞飞, 姜文剑, 张宏家, 赵远斐. 甲基巴多索龙在 BAPN 诱导小鼠主动脉夹层模型中的作用评估[J]. 首都医科大学学报, doi: 10.3969/j.issn.1006-7795.2026.01.018.

lLiu Zhou, Liang Jiajun, Liu Ruifei, Jiang Wenjian, Zhang Hongjia, Zhao Yuanfei. Evaluation of the role of bardoxolone methyl in BAPN-induced mouse aortic dissection mode[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2026.01.018.

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甲基巴多索龙在 BAPN 诱导小鼠主动脉夹层模型中的作用评估

Evaluation of the role of bardoxolone methyl in BAPN-induced mouse aortic dissection mode

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