糖尿病大血管并发症相关动物模型的构建与应用进展

doi:10.12092/j.issn.1009-2501.2026.08.013

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (8): 1127-1134.doi: 10.12092/j.issn.1009-2501.2026.08.013

• 综述与讲座 • 上一篇

糖尿病大血管并发症相关动物模型的构建与应用进展

杨玉洁¹^,²(), 张莉莉¹^,², 潘昕昀¹^,², 丁英鹏³^,*(), 王中群¹^,²^,*()

1. 江苏大学附属医院心内科，镇江 212000，江苏
2. 江苏大学心血管疾病研究所，镇江 212001，江苏
3. 常州金坛第一人民医院心内科，常州 213200，江苏

收稿日期:2025-12-14 修回日期:2026-02-08 出版日期:2026-08-26 发布日期:2026-09-09
通讯作者: 丁英鹏,王中群 E-mail:1328044834@qq.com;doctording0556@163.com;wangtsmc@126.com
作者简介:杨玉洁，女，硕士研究生，研究方向：糖尿病动脉粥样硬化。E-mail：1328044834@qq.com
基金资助:
国家自然科学基金（82370457）；江苏省重点研发计划（BE2022780）

Advances in the construction and application of animal models for diabetic macrovascular complications

Yujie YANG¹^,²(), Lili ZHANG¹^,², Xinyun PAN¹^,², Yingpeng DING³^,*(), Zhongqun WANG¹^,²^,*()

1. Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu, China
2. Institute of Cardiovascular Diseases, Jiangsu University, Zhenjiang 212001, Jiangsu, China
3. Department of Cardiology, Changzhou Jintan First People's Hospital, Changzhou 213200, Jiangsu, China

Received:2025-12-14 Revised:2026-02-08 Online:2026-08-26 Published:2026-09-09
Contact: Yingpeng DING,Zhongqun WANG E-mail:1328044834@qq.com;doctording0556@163.com;wangtsmc@126.com

摘要/Abstract

摘要：

糖尿病大血管并发症是糖尿病患者致残和死亡的主要原因，其核心病理特征在于长期代谢紊乱背景下动脉粥样硬化的加速进展及斑块不稳定性增加。动物模型在阐明糖尿病大血管并发症的发病机制及评价防治措施中具有重要作用。本文围绕糖尿病冠状动脉疾病、脑血管病变及外周动脉疾病等主要类型，对饮食诱导、化学诱导、基因修饰及联合干预等常用动物模型的构建方法、病理特征及应用现状进行综述，比较不同模型在模拟疾病表型和研究适用性方面的差异，并分析其局限性。旨在为糖尿病大血管并发症动物模型的合理选择与改进提供参考依据。

关键词: 糖尿病大血管并发症, 动脉粥样硬化, 动物模型

Abstract:

Diabetes-associated macrovascular complications constitute a principal source of disability and mortality among individuals with diabetes. The defining pathological hallmark of these complications is the accelerated development of atherosclerosis accompanied by heightened plaque instability, arising in the context of chronic metabolic dysregulation. Animal models are therefore indispensable for elucidating the underlying mechanisms of diabetic macrovascular disease and for rigorously assessing preventive and therapeutic interventions. This review concentrates on the major manifestations of diabetic macrovascular pathology, including coronary artery disease, cerebrovascular disease, and peripheral arterial disease. It provides a systematic synthesis of the construction strategies, pathological features, and current research applications of widely used animal models, encompassing diet-induced, chemically induced, genetically modified, and combined-intervention approaches. In addition, the review offers a comparative evaluation of these models with respect to their capacity to recapitulate disease phenotypes and their suitability for addressing specific research questions, while also critically examining their methodological limitations. Collectively, this work aims to inform the rational selection and refinement of animal models for the study of diabetic macrovascular complications.

Key words: diabetes-associated macrovascular complications, atherosclerosis, animal model

中图分类号:

杨玉洁, 张莉莉, 潘昕昀, 丁英鹏, 王中群. 糖尿病大血管并发症相关动物模型的构建与应用进展[J]. 中国临床药理学与治疗学, 2026, 31(8): 1127-1134.

Yujie YANG, Lili ZHANG, Xinyun PAN, Yingpeng DING, Zhongqun WANG. Advances in the construction and application of animal models for diabetic macrovascular complications[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1127-1134.

图/表 3

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物种	建模策略	主要心血管表型	模型优势	主要局限性	主要转化应用	参考文献
非人灵长类	STZ ±高脂饮食；自发性糖尿病	进展性动脉粥样硬化；心肌梗死	代谢及血管特征与人类最为接近	成本高；伦理限制严格	晚期转化研究	[5]
猪	高脂饮食 ± STZ；遗传性血脂异常模型	伴坏死核心及钙化的冠状动脉斑块	冠状动脉解剖结构与人类相似	诱导周期长；饲养与维护成本高	介入治疗及器械评价	[6]
兔	高胆固醇饮食 ± 血管损伤	富脂性动脉粥样硬化斑块	CETP 依赖的脂质代谢方式与人类相近	自发性冠状动脉受累有限	斑块生物学研究	[7]
小鼠	遗传模型；STZ + 高脂饮食	动脉粥样硬化；糖尿病性心肌病	重复性好；遗传操作性强	斑块破裂少见	机制性研究	[8]
大鼠	遗传或化学诱导	心肌损伤；轻度动脉粥样硬化	操作简便；代谢表型稳定	对动脉粥样硬化相对耐受	代谢–血管相互作用研究	[9]
斑马鱼	高糖或高脂环境饲养	心肌病变；血管脂质沉积	适于高通量研究；体内实时成像	缺乏自发性冠状动脉血栓形成	药物筛选及毒性评估	[10]

物种	建模策略	主要心血管表型	模型优势	主要局限性	主要转化应用	参考文献
非人灵长类	STZ ±高脂饮食；自发性糖尿病	进展性动脉粥样硬化；心肌梗死	代谢及血管特征与人类最为接近	成本高；伦理限制严格	晚期转化研究	[5]
猪	高脂饮食 ± STZ；遗传性血脂异常模型	伴坏死核心及钙化的冠状动脉斑块	冠状动脉解剖结构与人类相似	诱导周期长；饲养与维护成本高	介入治疗及器械评价	[6]
兔	高胆固醇饮食 ± 血管损伤	富脂性动脉粥样硬化斑块	CETP 依赖的脂质代谢方式与人类相近	自发性冠状动脉受累有限	斑块生物学研究	[7]
小鼠	遗传模型；STZ + 高脂饮食	动脉粥样硬化；糖尿病性心肌病	重复性好；遗传操作性强	斑块破裂少见	机制性研究	[8]
大鼠	遗传或化学诱导	心肌损伤；轻度动脉粥样硬化	操作简便；代谢表型稳定	对动脉粥样硬化相对耐受	代谢–血管相互作用研究	[9]
斑马鱼	高糖或高脂环境饲养	心肌病变；血管脂质沉积	适于高通量研究；体内实时成像	缺乏自发性冠状动脉血栓形成	药物筛选及毒性评估	[10]

模型	主要优势	主要局限性	典型研究用途	参考文献
短暂性大脑中动脉阻断模型（tMCAo）	缺血范围明确；半暗带可重复性好；可实现再灌注	个体间梗死体积差异较大；技术要求高；术后并发症较多	超急性期缺血性脑损伤机制；溶栓及神经保护干预的评价	[47]
光栓塞性脑梗死模型	重复性高；局灶性皮层损伤；无需开颅	缺乏真实半暗带；损伤局限于浅表皮层	微血管血栓形成机制；药物疗效的初步筛选	[48]
永久性大脑中动脉阻断模型（pMCAo）	手术操作简单、快速；围手术期死亡率低	缺乏再灌注成分；功能缺损较轻	慢性脑缺血；卒中后认知障碍及血管性痴呆研究	[49]
高脂饮食/链脲佐菌素（HFD/STZ）+ tMCAo	联合2型糖尿病代谢异常与急性缺血损伤；临床相关性高	诱导期较长；血糖异质性显著；需加强代谢监测	糖尿病加重卒中损伤机制；代谢—神经保护联合干预策略	[50]
db/db小鼠+ MCA阻断	稳定的高血糖与胰岛素抵抗状态；慢性低灌注	成本高；饲养条件要求高；易发生自发性微出血	糖尿病相关慢性脑血管损伤；代谢异常与神经退行性变相互作用	[51]

模型	主要优势	主要局限性	典型研究用途	参考文献
短暂性大脑中动脉阻断模型（tMCAo）	缺血范围明确；半暗带可重复性好；可实现再灌注	个体间梗死体积差异较大；技术要求高；术后并发症较多	超急性期缺血性脑损伤机制；溶栓及神经保护干预的评价	[47]
光栓塞性脑梗死模型	重复性高；局灶性皮层损伤；无需开颅	缺乏真实半暗带；损伤局限于浅表皮层	微血管血栓形成机制；药物疗效的初步筛选	[48]
永久性大脑中动脉阻断模型（pMCAo）	手术操作简单、快速；围手术期死亡率低	缺乏再灌注成分；功能缺损较轻	慢性脑缺血；卒中后认知障碍及血管性痴呆研究	[49]
高脂饮食/链脲佐菌素（HFD/STZ）+ tMCAo	联合2型糖尿病代谢异常与急性缺血损伤；临床相关性高	诱导期较长；血糖异质性显著；需加强代谢监测	糖尿病加重卒中损伤机制；代谢—神经保护联合干预策略	[50]
db/db小鼠+ MCA阻断	稳定的高血糖与胰岛素抵抗状态；慢性低灌注	成本高；饲养条件要求高；易发生自发性微出血	糖尿病相关慢性脑血管损伤；代谢异常与神经退行性变相互作用	[51]

研究目的	优选模型	主要优势	主要局限性	推荐主要终点指标	参考文献
分子机制研究（血管生成、氧化应激等）	db/db 小鼠 + 股动脉结扎（FAL）	高血糖状态稳定；遗传背景一致；转基因与基因修饰工具成熟	缺乏明确动脉粥样硬化病变；年轻小鼠再灌注恢复较快	缺血侧/对侧足部灌注比值（激光多普勒）	[58]
动脉粥样硬化驱动的 PAD	STZ 处理的 C57BL/6 小鼠 + FAL	内皮功能障碍与斑块性狭窄并存；脂质代谢特征更接近人类 T2DM-PAD	需联合高脂饮食；建模周期较长、成本较高	斑块负荷–灌注复合评分	[59]
影像学评估及干预手段验证	四氧嘧啶（alloxan） + 高胆固醇饮食 + FAL（兔）	血管口径较大；影像学评估流程（CT/DSA/超声）与临床高度一致	需长期高胆固醇喂养；阿洛糖具有一定肾毒性	第21天 CT 评估 Rutherford 分级 ≥3	[7]
腔内介入器械评价	STZ + 球囊损伤（猪）	动脉直径接近人类；适用于导管及介入器械操作	成本高；实验室应用与验证相对有限	血管造影通畅率及再狭窄程度	[60]

糖尿病大血管并发症相关动物模型的构建与应用进展

Advances in the construction and application of animal models for diabetic macrovascular complications

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