中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (14): 2194-2199.doi: 10.12307/2023.164

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

博来霉素联合血管紧张素Ⅱ建立小鼠主动脉夹层模型

杨丽娟1,姚  娜2,鲁睿文2,刘晓宇2,王宝军1   

  1. 1包头市中心医院,内蒙古自治区包头市    014040;2包头医学院,内蒙古自治区包头市    014060
  • 收稿日期:2022-03-01 接受日期:2022-05-19 出版日期:2023-05-18 发布日期:2022-09-30
  • 通讯作者: 王宝军,博士,主任医师,包头市中心医院,内蒙古自治区包头市 014040
  • 作者简介:杨丽娟,女,1979年生,内蒙古自治区包头市人,汉族,2018年重庆医科大学毕业,博士, 主任医师,主要从事脑血管疾病诊疗方面的研究。
  • 基金资助:
    内蒙古自然科学基金(2020MS08065),项目负责人:杨丽娟

Bleomycin combined with angiotensin II for establishing a mouse model of aortic dissection

Yang Lijuan1, Yao Na2, Lu Ruiwen2, Liu Xiaoyu2, Wang Baojun1   

  1. 1Baotou Central Hospital, Baotou 014040, Inner Mongolia Autonomous Region, China; 2Baotou Medical College, Baotou 014060, Inner Mongolia Autonomous Region, China
  • Received:2022-03-01 Accepted:2022-05-19 Online:2023-05-18 Published:2022-09-30
  • Contact: Wang Baojun, MD, Chief physician, Baotou Central Hospital, Baotou 014040, Inner Mongolia Autonomous Region, China
  • About author:Yang Lijuan, MD, Chief physician, Baotou Central Hospital, Baotou 014040, Inner Mongolia Autonomous Region, China
  • Supported by:
    the Natural Science Foundation of Inner Mongolia Autonomous Region, No. 2020MS08065 (to YLJ)

摘要:

文题释义:
主动脉非炎性退行性变:描述主动脉中膜退行性改变的规范化病理学术语,它的定义就是由非炎性病变而是个体的组织病理变性导致的主动脉中膜的病变或损伤,在组织病理切片(苏木精-伊红染色和其他能显示弹性纤维和细胞外基质材料的染色法)上可观察到,主要受累部位是动脉中膜的板层单元结构(包括细胞和细胞外结构)。

背景:主动脉夹层是一种少见疾病,发病凶险、死亡率高,目前其发病机制仍不完全清楚,对其发病机制进行研究将有重要的临床意义。
目的:采用博来霉素联合血管紧张素Ⅱ构建小鼠主动脉夹层的模型,探讨存在结缔组织疾病的小鼠是否更具发生动脉夹层的病理学基础。
方法:选取24只雌性BALB/c小鼠,按随机数字表法随机分成实验组和对照组,每组12只。实验组小鼠首先背部皮下注射博莱霉素构建系统性硬化病模型,对照组背部皮下注射等量无菌PBS,连续注射3周。检测两组小鼠尿液羟脯氨酸水平、背部皮肤厚度及体质量指标验证造模是否成功,系统性硬化病造模成功后7 d,两组小鼠腹腔注射血管紧张素Ⅱ构建主动脉夹层模型,持续注射14 d。造模后分析两组小鼠主动脉中膜非炎性退行性变的程度并进行半定量分级。
结果与结论:①与对照组小鼠比较,实验组小鼠尿液羟脯氨酸水平明显增多,背部皮肤厚度明显增加,体质量明显降低,差异均有显著性意义(P < 0.05);②两组小鼠在腹腔注射血管紧张素Ⅱ 30 min后,收缩压、舒张期及平均动脉压差异均无显著性意义(P > 0.05);③与对照组小鼠相比,实验组小鼠主动脉中膜非炎性退行性变的严重程度显著增高,差异有显著性意义(P < 0.05);④以上结果表明,用博来霉素联合血管紧张素Ⅱ构建的主动脉夹层小鼠模型,主动脉中膜非炎性退行性变比较严重,与对照组小鼠相比更具发生动脉夹层的病理学基础。

https://orcid.org/0000-0001-8010-9193(杨丽娟);https://orcid.org/0000-0002-9893-8050 (王宝军) 

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 博来霉素, 血管紧张素Ⅱ, 系统性硬化病, 主动脉中膜非炎性退行性变, 主动脉夹层, 结缔组织疾病

Abstract: BACKGROUND: Aortic dissection is a rare life-threatening disease with high mortality. At present, the pathogenesis of aortic dissection is still not fully understood; therefore, research on its pathogenesis will have important clinical significance.
OBJECTIVE: To investigate the pathological basis of arterial dissection in mice with connective tissue disease through constructing an aortic dissection model by bleomycin combined with angiotensin II.
METHODS: Twenty-four female BALB/c mice were randomly divided into control group and experimental group, with twelve mice in each group. Mice in the experimental group were subcutaneously treated with bleomycin to establish a systemic sclerosis model, while those in the control group were treated with phosphate buffered saline. Administration in each group lasted for 3 weeks. Mice in the two groups were examined for urine hydroxyproline level, back skin thickness and body mass to verify whether the model was successfully established. Mice were intraperitoneally injected angiotensin II beginning at 7 days after modeling for 14 continuous days. The histopathological changes in the aortic media of the two groups were analyzed and semi-quantitative grading was performed after modeling.
RESULTS AND CONCLUSION: There were significant increases in the urine hydroxyproline level and back skin thickness and a significant reduction in body mass in the experimental group compared with the control group (P < 0.05). There were no significant differences in systolic pressure, diastolic stage and mean arterial pressure between the two groups at 30 minutes after intraperitoneal injection of angiotensin II (P > 0.05). Compared with the control group, mice in the experimental group presented with significantly severer non-inflammatory degenerative lesions of the aortic media (P < 0.05). All findings indicate that non-inflammatory degeneration of the aortic media is more serious in the experimental mice then the control mice, that is, experimental mice are more prone to arterial dissection pathologically.

Key words: bleomycin, angiotensin II, systemic sclerosis, non-inflammatory degeneration of the aortic media, aortic dissection, connective tissue disease

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