脑卒中动物模型构建与评价方法评述

doi:10.12300/j.issn.1674-5817.2025.037

实验动物与比较医学 ›› 2026, Vol. 46 ›› Issue (1): 94-106.DOI: 10.12300/j.issn.1674-5817.2025.037

脑卒中动物模型构建与评价方法评述

杨韵蓉¹(), 吴文郁², 谭跃³, 严国锋⁴, 李垚⁴, 卢今⁴()()

^1.上海交通大学医学院医疗门诊部, 上海 200025
^2.上海交通大学医学院全球健康学院, 上海 200025
^3.上海中医药大学附属市中医医院脑病科, 上海 200040
^4.上海交通大学医学院实验动物科学部, 上海 200025

收稿日期:2025-03-13 修回日期:2025-12-29 出版日期:2026-02-25 发布日期:2026-02-14
通讯作者: 卢今（1990—），女，博士研究生，兽医师，研究方向：实验动物影像学、实验动物模型。E-mail：ashleelu@shsmu.edu.cn。ORCID：0009-0000-7740-7915
作者简介:杨韵蓉（1996—），女，硕士，医师，研究方向：脑卒中的机制研究。E-mail：605298878@qq.com。ORCID：0009-0003-3561-3536
基金资助:
上海交通大学医学院科技创新项目“全球‘全健康’理念对公共卫生事业发展的研究”(WK2406);上海高校教师产学研践习计划项目(BJ1-3000-24-0067)

A Review of Methods for Establishing and Evaluating Animal Models of Stroke

YANG Yunrong¹(), WU Wenyu², TAN Yue³, YAN Guofeng⁴, LI Yao⁴, LU Jin⁴()()

^1.Outpatient Department, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
^2.School of Global Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
^3.Department of Encephalopathy, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200040, China
^4.Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2025-03-13 Revised:2025-12-29 Published:2026-02-25 Online:2026-02-14
Contact: LU Jin (ORCID: 0009-0000-7740-7915), E-mail: ashleelu@shsmu.edu.cn

摘要/Abstract

摘要：

脑卒中作为全球范围内主要的致残与致死病因之一，其机制研究与治疗策略开发高度依赖于能够准确模拟人类疾病病理特征的动物模型。理想的脑卒中动物模型不仅需要再现临床上患者发生脑卒中后的神经功能缺损与病理变化，还应具备良好的可重复性与转化价值。本文围绕缺血性脑卒中动物模型的制备和评价方法展开论述：首先，阐述了啮齿类（大鼠、小鼠）及非啮齿类（非人灵长类、小型猪、兔、斑马鱼）等实验动物的选择依据及其优劣；其次，详细综述了缺血性脑卒中模型与出血性脑卒中模型的造模原理、操作要点及适用范围；紧接着，本文综述了基因编辑［如规律成簇的间隔短回文重复序列（clustered regularly interspaced short palindromic repeats，CRISPR）/CRISPR相关蛋白9（CRISPR-associated protein 9，Cas9）基因编辑技术］、多模态成像（如双光子显微、光声成像）、人工智能、光遗传学、3D生物打印、类器官模型及多组学等新兴技术在脑卒中动物模型构建优化、精准评估与机制研究中的应用进展；最后，本文通过系统性分析2019—2024年间国内外相关研究文献，探讨了基于研究目标的模型选择策略，涵盖行为学、影像学及分子病理学的多维评价体系，并展望了未来通过技术融合实现模型精准化与个体化的发展方向。本文旨在提供全面的方法学参考，帮助研究者根据具体科学问题选择合适的脑卒中动物模型。

关键词: 脑卒中, 动物模型, 缺血性脑卒中, 出血性脑卒中, 造模方法, 模型优化

Abstract:

Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies,including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

Key words: Stroke, Animal model, Ischemic stroke, Hemorrhagic stroke, Modeling methods, Model optimization

中图分类号:

R-332

杨韵蓉,吴文郁,谭跃,等. 脑卒中动物模型构建与评价方法评述[J]. 实验动物与比较医学, 2026, 46(1): 94-106. DOI: 10.12300/j.issn.1674-5817.2025.037.

YANG Yunrong,WU Wenyu,TAN Yue,et al. A Review of Methods for Establishing and Evaluating Animal Models of Stroke[J]. Laboratory Animal and Comparative Medicine, 2026, 46(1): 94-106. DOI: 10.12300/j.issn.1674-5817.2025.037.

图/表 4

参考文献 76

[1]	石沪娟, 夏一航, 程怡然, 等. 1990年至2049年全球脑卒中疾病负担分析及预测[J]. 中国医学装备, 2024, 21(11): 141-150. DOI: 10.3969/j.issn.1672-8270.2024.11.027 .
	SHI H J, XIA Y H, CHENG Y R, et al. Analysis and prediction of global burden of stroke diseases from 1990 to 2049[J]. China Med Equip, 2024, 21(11): 141-150. DOI: 10.3969/j.issn.1672-8270.2024.11.027 .
[2]	SAINI V, GUADA L, YAVAGAL D R. Global epidemiology of stroke and access to acute ischemic stroke interventions[J]. Neurology, 2021, 97(20 ): S6-S16. DOI: 10.1212/WNL. 0000000000012781 .
[3]	BARTHELS D, DAS H. Current advances in ischemic stroke research and therapies[J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(4): 165260. DOI: 10.1016/j.bbadis.2018.09.012 .
[4]	CAMPBELL B C V, DE SILVA D A, MACLEOD M R, et al. Ischaemic stroke[J]. Nat Rev Dis Primers, 2019, 5: 70. DOI: 10. 1038/s41572-019-0118-8 .
[5]	HILKENS N A, CASOLLA B, LEUNG T W, et al. Stroke[J]. Lancet, 2024, 403(10446): 2820-2836. DOI: 10.1016/S0140-6736(24)00642-1 .
[6]	ZHAO Y F, ZHANG X J, CHEN X Y, et al. Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review)[J]. Int J Mol Med, 2022, 49(2): 1-9. DOI: 10.3892/ijmm.2021.5070 DOI: 10.3892/ijmm.2021.5070 .
[7]	TU W J, WANG L D, YAN F, et al. China stroke surveillance report 2021[J]. Mil Med Res, 2023, 10(1): 1-26. DOI: 10.1186/s40779-023-00463-x .
[8]	LEE E C, HA T W, LEE D H, et al. Utility of exosomes in ischemic and hemorrhagic stroke diagnosis and treatment[J]. Int J Mol Sci, 2022, 23(15): 8367. DOI: 10.3390/ijms2315 8367 .
[9]	RIGUAL R, FUENTES B, DÍEZ-TEJEDOR E. Management of acute ischemic stroke[J]. Med Clínica(Engl Ed), 2023, 161(11): 485-492. DOI: 10.1016/j.medcle.2023.06.032 .
[10]	KURIAKOSE D, XIAO Z C. Pathophysiology and treatment of stroke: present status and future perspectives[J]. Int J Mol Sci, 2020, 21(20): 7609. DOI: 10.3390/ijms21207609 .
[11]	沈亚亭, 白秀, 王明威, 等. 啮齿类动物局灶性脑缺血模型研究进展[J]. 河北医药, 2021, 43(17): 2673-2677, 2683. DOI: 10.3969/j.issn.1002-7386.2021.17.029 .
	SHEN Y T, BAI X, WANG M W, et al. Research progress of focal cerebral ischemia models in rodents[J]. Hebei Med J, 2021, 43(17): 2673-2677, 2683. DOI: 10.3969/j.issn.1002-7386.2021.17.029 .
[12]	郭春晓, 黄鹤. 木犀草素调控海马小胶质细胞极化改善脑卒中大鼠神经元功能[J]. 解剖科学进展, 2025, 31(4): 489-492, 497. DOI: 10.16695/j.cnki.1006-2947.2025.04.011 .
	GUO C X, HUANG H. Luteolin regulates microglia polarization in hippocampus to improve neuronal function in stroke rats[J]. Prog Anat Sci, 2025, 31(4): 489-492, 497. DOI: 10.16695/j.cnki.1006-2947.2025.04.011 .
[13]	SOMMER C J. Ischemic stroke: experimental models and reality[J]. Acta Neuropathol, 2017, 133(2): 245-261. DOI: 10.1007/s00401-017-1667-0 .
[14]	TIAN R L, GACHECHILADZE M A, LUDWIG C H, et al. CRISPR interference-based platform for multimodal genetic screens in human iPSC-derived neurons[J]. Neuron, 2019, 104(2): 239-255.e12. DOI: 10.1016/j.neuron.2019.07.014 .
[15]	WANG S W, GAO C, ZHENG Y M, et al. Current applications and future perspective of CRISPR/Cas9 gene editing in cancer[J]. Mol Cancer, 2022, 21(1): 57. DOI: 10.1186/s12943-022-01518-8 .
[16]	LIN Y T, SEO J, GAO F, et al. APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC-derived brain cell types[J]. Neuron, 2018, 98(6): 1141-1154.e7. DOI: 10.1016/j.neuron.2018.05.008 .
[17]	AYGAR S, DAHERON L. Generation of a human iPSC line with Notch3 R133C mutation by CRISPR/Cas9: a tool for investigating CADASIL and therapeutic targets[J]. Stem Cell Res, 2025, 84: 103678. DOI: 10.1016/j.scr.2025.103678 .
[18]	KEAT WEI L, GRIFFITHS L R, IRENE L, et al. Association of NOTCH3 gene polymorphisms with ischemic stroke and its subtypes: a meta-analysis[J]. Medicina, 2019, 55(7): 351. DOI: 10.3390/medicina55070351 .
[19]	MONTAGNE A, NATION D A, ZLOKOVIC B V. APOE4 accelerates development of dementia after stroke: is there a role for cerebrovascular dysfunction?[J]. Stroke, 2020, 51(3): 699-700. DOI: 10.1161/STROKEAHA.119.028814 .
[20]	陈秋燕, 许宵钰, 周靓, 等. 慢性脑低灌注实验动物模型的研究进展[J]. 中国药学杂志, 2025, 60(14): 1472-1478. DOI: 10.11669/cpj.2025.14.004 .
	CHEN Q Y, XU X Y, ZHOU L, et al. Research progress of experimental animal models of chronic cerebral hypoperfusion[J]. Chin Pharm J, 2025, 60(14): 1472-1478. DOI: 10.11669/cpj.2025.14.004 .
[21]	孙宇航, 管博文, 魏强, 等. 缺血性脑卒中非人灵长类动物模型研究进展[J]. 中国比较医学杂志, 2022, 32(8): 123-130. DOI: 10.3969/j.issn.1671-7856.2022.08.017 .
	SUN Y H, GUAN B W, WEI Q, et al. Research progress of non-human primate model of ischemic stroke[J]. Chin J Comp Med, 2022, 32(8): 123-130. DOI: 10.3969/j.issn.1671-7856.2022.08.017 .
[22]	叶娟, 尚海龙, 沈海林, 等. DSA引导下食蟹猴大脑中动脉栓塞模型的建立与评价[J]. 介入放射学杂志, 2022, 31(4): 369-373. DOI: 10.3969/j.issn.1008-794X.2022.04.010 .
	YE J, SHANG H L, SHEN H L, et al. Establishment of DSA-guided middle cerebral artery embolization mode in cynomolgus monkeys and its technical evaluation[J]. J Interv Radiol, 2022, 31(4): 369-373. DOI: 10.3969/j.issn.1008-794X.2022.04.010 .
[23]	刘柘君, 唐田, 谭天阳, 等. 缺血性脑卒中模型研究进展[J]. 中国药物警戒, 2024, 21(12): 1393-1397, 1404. DOI: 10.19803/j.1672-8629.20240637 .
	LIU Z J, TANG T, TAN T Y, et al. Research progress on models of ischemic stroke[J]. Chin J Pharmacovigil, 2024, 21(12): 1393-1397, 1404. DOI: 10.19803/j.1672-8629.20240637 .
[24]	刘宇, 魏泓. 小型猪心血管系统疾病动物模型研究现状及趋势[J]. 实验动物与比较医学, 2011, 31(5): 322-329. DOI: 10.3969/j.issn.1674-5817.2011.05.004 .
	LIU Y, WEI H. Research status and trend of animal models of cardiovascular diseases in miniature pigs[J]. Lab Anim Comp Med, 2011, 31(5): 322-329. DOI: 10.3969/j.issn.1674-5817.2011.05.004 .
[25]	王静. 血管超声评估兔急性颈动脉血栓模型及诱发缺血性脑卒中的实验研究[D].苏州: 苏州大学, 2020.DOI:10.27351/d .
	WANG J. Vascular ultrasound evaluation of a rabbit model of acute carotid artery thrombosis and its induction of ischemic stroke[D]. Suzhou: soochow university, 2020. DOI:10.27351/d .
[26]	王静, 杨德斌, 姚晓华, 等. Fecl₃诱导兔颈动脉血栓形成建立缺血性脑卒中模型的实验研究[J]. 中国超声医学杂志, 2019, 35(9): 853-856. DOI: 10.3969/j.issn.1002-0101.2019.09.026 .
	WANG J, YANG D B, YAO X H, et al. Experimental study on establishment of ischemic stroke rabbit model induced by Fecl₃ in carotid artery thrombosis[J]. Chin J Ultrasound Med, 2019, 35(9): 853-856. DOI: 10.3969/j.issn.1002-0101.2019.09.026 .
[27]	吴慧敏. 基于斑马鱼模型的谷红注射液抗缺血性脑卒中药效作用及质量评价研究[D]. 杭州: 浙江大学, 2022.10.27461. DOI: /d.cnki.gzjdx.2022.001377 .
	WU H M. Study on the Pharmacodynamic effects and quality evaluation of guhong injection against ischemic stroke based on a zebrafish model[D]. Hangzhou: Zhejiang University, 2022. DOI:10.27461/d.cnki.gzjdx.2022.001377 .
[28]	樊午阳, 王琴梅. 1-苯基-2-硫脲抑制flk1型斑马鱼黑色素生成的最佳浓度[J]. 中山大学学报(医学科学版), 2016, 37(2): 161-167. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2016.0030 .
	FAN W Y, WANG Q M. Optimal concentration of 1-phenyl 2-thiourea for inhibiting melanogenesis in flk1 zebrafish[J]. J Sun Yat Sen Univ(Med Sci), 2016, 37(2): 161-167. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2016.0030 .
[29]	许娜, 渠静, 王赛楠, 等. 老年大鼠大脑中动脉永久性缺血与缺血再灌注对大脑损伤的比较研究[J]. 中国现代医学杂志, 2019, 29(16): 17-21. DOI: 10.3969/j.issn.1005-8982.2019.16.003 .
	XU N, QU J, WANG S N, et al. Comparison of middle cerebral artery permanent ischemia and ischemia reperfusion in aged rats[J]. China J Mod Med, 2019, 29(16): 17-21. DOI: 10.3969/j.issn.1005-8982.2019.16.003 .
[30]	展淑琴, 高亚亚, 张凌峰, 等. 大鼠大脑中动脉永久性缺血和缺血再灌注模型的比较[J]. 陕西医学杂志, 2013, 42(6): 643-646. DOI: 10.3969/j.issn.1000-7377.2013.06.001 .
	ZHAN S Q, GAO Y Y, ZHANG L F, et al. The comparison between permanent middle cerebral artery occlusion model and the model of ischemia reperfusion in middle cerebral artery occlusion[J]. Shaanxi Med J, 2013, 42(6): 643-646. DOI: 10.3969/j.issn.1000-7377.2013.06.001 .
[31]	MCBRIDE D W, ZHANG J H. Precision stroke animal models: the permanent MCAO model should be the primary model, not transient MCAO[J]. Transl Stroke Res, 2017: 397-404. DOI: 10.1007/s12975-017-0554-2 .
[32]	刘红梅, 高天明, 佟振清. 急性脑缺血动物模型实验研究进展[J]. 第一军医大学学报, 1999, 19(4): 368-370. DOI: 10.3321/j.issn: 1673-4254.1999.04.035 .
	LIU H M, GAO T M, TONG Z Q. Experimental research progress of acute cerebral ischemia animal model[J]. J First Mil Med Univ, 1999, 19(4): 368-370. DOI: 10.3321/j.issn: 1673-4254.1999.04.035 .
[33]	邓敏贞, 钟晓琴, 高志杰, 等. 益脑康胶囊对缺血再灌注模型小鼠自噬相关因子Beclin-1、LC3B和p62的影响[J]. 西部中医药, 2023, 36(9): 10-14. DOI: 10.12174/j.issn.2096-9600.2023.09.03 .
	DENG M Z, ZHONG X Q, GAO Z J, et al. Effects of yinaokang capsules on autophagy-related factors beclin-1, LC3B and p62 in mice model of ischemia reperfusion[J]. West J Tradit Chin Med, 2023, 36(9): 10-14. DOI: 10.12174/j.issn.2096-9600.2023.09.03 .
[34]	吴远华, 朱广旗, 胡蓉, 等. 线栓法大鼠脑缺血再灌注模型改良与评价[J]. 中国实用神经疾病杂志, 2010, 13(18): 4-6. DOI: 10.3969/j.issn.1673-5110.2010.18.002 .
	WU Y H, ZHU G Q, HU R, et al. Improvement and evaluation on rat ischemia-reperfusion injury model with string-fastening method[J]. Chin J Pract Nerv Dis, 2010, 13(18): 4-6. DOI: 10.3969/j.issn.1673-5110.2010.18.002 .
[35]	LIANG X, QUAN X P, GENG X R, et al. A promising approach for quantifying focal stroke modeling and assessing stroke progression: optical resolution photoacoustic microscopy photothrombosis[J]. Neural Regen Res, 2025, 20(7): 2029-2037. DOI: 10.4103/NRR.NRR-D-23-01617 .
[36]	ZHANG H Y, ZHAO Z Q, SUN S N, et al. Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke[J]. Nat Commun, 2023, 14: 255. DOI: 10.1038/s41467-023-35895-5 .
[37]	KALYUZHNAYA Y N, KHAITIN A M, DEMYANENKO S V. Modeling transient ischemic attack via photothrombosis[J]. Biophys Rev, 2023, 15(5): 1279-1286. DOI: 10.1007/s12551-023-01121-1 .
[38]	DELAFONTAINE-MARTEL P, ZHANG C, LU X C, et al. Targeted capillary photothrombosis via multiphoton excitation of Rose Bengal[J]. J Cereb Blood Flow Metab, 2023, 43(10): 1713-1725. DOI: 10.1177/0271678X231151560 .
[39]	MAURITZON S, GINSTMAN F, HILLMAN J, et al. Analysis of laser Doppler flowmetry long-term recordings for investi-gation of cerebral microcirculation during neurointensive care[J]. Front Neurosci, 2022, 16: 1030805. DOI: 10.3389/fnins. 2022.1030805 .
[40]	ZHU X, YI Z C, LI R L, et al. Constructing a transient ischemia attack model utilizing flexible spatial targeting photothrombosis with real-time blood flow imaging feedback[J]. Int J Mol Sci, 2024, 25(14): 7557. DOI: 10.3390/ijms25147557 .
[41]	LIU K T, WANG P W, HSIEH H Y, et al. Site-specific thrombus formation: advancements in photothrombosis-on-a-chip technology[J]. Lab Chip, 2024, 24(14): 3422-3433.
[42]	李建生, 刘敬霞, 于海滨, 等. 大鼠自体血栓结合线栓阻塞大脑中动脉制备脑缺血模型的建立与评价[J]. 中国危重病急救医学, 2006, 18(5): 272-274. DOI: 10.3760/j.issn: 1003-0603.2006.05.005 .
	LI J S, LIU J X, YU H B, et al. Establishment and evaluation of reproduction of middle cerebral artery occlusion to produce cerebral ischemia with autologous blood clot and nylon thread in rat[J]. Chin Crit Care Med, 2006, 18(5): 272-274. DOI: 10.3760/j.issn: 1003-0603.2006.05.005 .
[43]	周光兴, 高诚, 徐平, 等. 人类疾病动物模型复制方法学[M]. 上海: 上海科学技术文献出版社, 2007.
	ZHOU G X, GAO C, XU P, et al. Reproduction Methodology of animal models for human diseases[M]. Shanghai: Shanghai Scientific and Technological Literature Press, 2007.
[44]	沈志勇, 王锋. 康脑灵胶囊对血管性痴呆模型大鼠体内自由基代谢影响的研究[J]. 中国实用医药, 2008, 3(29): 82-84. DOI: 10.14163/j.cnki.11-5547/r.2008.29.032 .
	SHEN Z Y, WANG F. Effect of kangnaoling capsule on free radical metabolism in vascular dementia model rats[J]. China Pract Med, 2008, 3(29): 82-84. DOI: 10.14163/j.cnki.11-5547/r.2008.29.032 .
[45]	SOUTH K, SALEH O, LEMARCHAND E, et al. Robust thrombolytic and anti-inflammatory action of a constitutively active ADAMTS13 variant in murine stroke models[J]. Blood, 2022, 139(10): 1575-1587. DOI: 10.1182/blood.2021012787 .
[46]	KARATAS H, JUNG J EUN, LO E H, et al. Inhibiting 12/15-lipoxygenase to treat acute stroke in permanent and tPA induced thrombolysis models[J]. Brain Res, 2018, 1678: 123-128. DOI: 10.1016/j.brainres.2017.10.024 .
[47]	NANRI M, WATANABE H. Availability of 2VO rats as a model for chronic cerebrovascular disease[J]. Nihon Yakurigaku Zasshi, 1999, 113(2): 85-95. DOI: 10.1254/fpj.113.85 .
[48]	SANI A F, WIDJIATI W, SUGIANTO P, et al. Bilateral asymptomatic common carotid artery stenosis: Mouse model for stroke research[J]. Open Vet J, 2022, 12(4): 463-468. DOI: 10.5455/OVJ.2022.v12.i4.7 .
[49]	KOZA Y, BAYRAM E, AYDIN M D, et al. Predictive role of the cervical sympathetic trunk ischemia on lower heart rates in an experimentally induced stenoocclusive carotid artery model by bilateral common carotid artery ligation[J]. Cardiovasc Toxicol, 2019, 19(1): 56-61. DOI: 10.1007/s12012-018-9473-z .
[50]	CICEK I, SOMUNCU A M, ALTUNER D, et al. Lacidipine, thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation[J]. Int J Ophthalmol, 2024, 17(5): 815-821. DOI: 10.18240/ijo.2024.05.04 .
[51]	AYDIN M D, KANAT A, AYDIN A, et al. Estimating basilar artery upper rupture limit by dangerous alarming diameter of arteries (DADA) following bilateral common carotid artery ligation; a new theorem[J]. Int J Neurosci, 2022, 132(2): 107-113. DOI: 10.1080/00207454.2020.1803303 .
[52]	WANG Y, TIAN M, TAN J Y, et al. Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin αVβ5/AMPK signaling pathway after intracerebral hemorrhage in mice[J]. J Neuroinflammation, 2022, 19(1): 82. DOI: 10.1186/s12974-022-02438-6 .
[53]	YANG M X, DENG S X, JIANG J L, et al. Oxytocin improves intracerebral hemorrhage outcomes by suppressing neuronal pyroptosis and mitochondrial fission[J]. Stroke, 2023, 54(7): 1888-1900. DOI: 10.1161/STROKEAHA.123.043391 .
[54]	THANGAMEERAN S I M, PANG C Y, LEE C H, et al. Experimental animal models and evaluation techniques in intracerebral hemorrhage[J]. Tzu Chi Med J, 2023, 35(1): 1-10. DOI: 10.4103/tcmj.tcmj_119_22 .
[55]	FANG J, SONG F L, CHANG C Q, et al. Intracerebral hemorrhage models and behavioral tests in rodents[J]. Neuroscience, 2023, 513: 1-13. DOI: 10.1016/j.neuroscience. 2023.01.011 .
[56]	SHI Z M, JING J J, XUE Z J, et al. Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke[J]. J Neuro-inflammation, 2023, 20(1): 82. DOI: 10.1186/s12974-023-02765-2 .
[57]	孔维麟. 急性缺血性卒中血管内治疗无效再通影响因素分析与干预策略研究[D]. 重庆: 中国人民解放军陆军军医大学, 2023. DOI:10.27001/d.cnki.gtjyu.2023.000073 .
	KONG W L. Studies of factors analysis and intervention strategies offutile recanalization following endovascular therapy foracute ischemic stroke[D]. Chongqing: Army Medical University, 2023. DOI: 10.27001/d.cnki.gtjyu.2023.000073 .
[58]	思宇涛, 尹琳, 马春野, 等. 前后循环大血管闭塞型缺血性脑卒中血管成功再通后临床预后的比较[J]. 中华神经医学杂志, 2023, 22(10): 1016-1022. DOI: 10.3760/cma.j.cn115354-20230824-00082 .
	SI Y T, YIN L, MA C Y, et al. Comparison of clinical prognoses of anterior and posterior circulatory large vessel occlusive ischemic stroke after successful endovascular recanalization[J]. Chin J Nburomedicine, 2023, 22(10): 1016-1022. DOI: 10.3760/cma.j.cn115354-20230824-00082 .
[59]	SEKER F, QURESHI M M, MÖHLENBRUCH M A, et al. Reperfusion without functional independence in late presentation of stroke with large vessel occlusion[J]. Stroke, 2022, 53(12): 3594-3604. DOI: 10.1161/STROKEAHA.122.039476 .
[60]	LOPEZ-RIVERA V, SALAZAR-MARIONI S, ABDELKHALEQ R, et al. Integrated stroke system model expands availability of endovascular therapy while maintaining quality outcomes[J]. Stroke, 2021, 52(3): 1022-1029. DOI: 10.1161/STROKEAHA. 120.032710 .
[61]	AHMED S, TRIPATHY R K, PANDE A H, et al. Neuroprotective potential of ApoE-mimetic peptide (ApoEFrag) in stroke models: Neurobehavioural and mechanistic study[J]. Int J Biol Macromol, 2025, 304(Pt 2): 140790. DOI: 10.1016/j.ijbiomac.2025.140790 .
[62]	李颖, 黄乐乐, 黄枫, 等. 近10年虚拟现实技术在脑卒中领域应用的可视化分析[J]. 海军军医大学学报, 2025, 46(4): 458-465. DOI: 10.16781/j.CN31-2187/R.20250047 .
	LI Y, HUANG L L, HUANG F, et al. Application of virtual reality technology in stroke field over the past decade: a visualization analysis[J]. Acad J Nav Med Univ, 2025, 46(4): 458-465. DOI: 10.16781/j.CN31-2187/R.20250047 .
[63]	ZHU J, MO J Y, LIU K W, et al. Glymphatic system impairment contributes to the formation of brain edema after ischemic stroke[J]. Stroke, 2024, 55(5): 1393-1404. DOI: 10.1161/STROKEAHA.123.045941 .
[64]	SKROBOT M, DE SA R, WALTER J, et al. Refined movement analysis in the staircase test reveals differential motor deficits in mouse models of stroke[J]. J Cereb Blood Flow Metab, 2024, 44(9): 1551-1564. DOI: 10.1177/0271678X241254718 .
[65]	CUI L Y, FAN Z Y, YANG Y J, et al. Deep learning in ischemic stroke imaging analysis: a comprehensive review[J]. Biomed Res Int, 2022, 2022: 2456550. DOI: 10.1155/2022/2456550 .
[66]	LI Y Y, ZHANG J J. Animal models of stroke[J]. Anim Models Exp Med, 2021, 4(3): 204-219. DOI: 10.1002/ame2.12179 .
[67]	BO B, LI Y, LI W L, et al. Neurovascular coupling impairment in acute ischemic stroke by optogenetics and optical brain imaging[J]. Annu Int Conf IEEE Eng Med Biol Soc, 2020, 2020: 3727-3730. DOI: 10.1109/EMBC44109.2020.9176641 .
[68]	LI S M, LI Y H, HUANG P C, et al. Knockout of Rnf213 ameliorates cerebral ischemic-reperfusion injury by inhibiting neuronal apoptosis through the Akt/GSK-3β/β-catenin/bcl-2 pathway[J]. Neuroscience, 2023, 533: 10-21. DOI: 10.1016/j.neuroscience.2023.09.018 .
[69]	HASAN K M, HAQUE M E. Editorial for "predicting the onset of ischemic stroke with fast high-resolution 3D MR spectroscopic imaging"[J]. J Magn Reson Imaging, 2023, 58(3): 848-849. DOI: 10.1002/jmri.28592 .
[70]	DING R L, ZHANG H. Effects of magnetic nanoparticle drug delivery systems on thrombosis and neuroprotection in brain stroke model[J]. J Nanosci Nanotechnol, 2021, 21(2): 859-867. DOI: 10.1166/jnn.2021.18654 .
[71]	ZHAO L Q, CHEN Y, LI H X, et al. Deciphering the neuroprotective mechanisms of RACK1 in cerebral ischemia-reperfusion injury: Pioneering insights into mitochondrial autophagy and the PINK1/Parkin axis[J]. CNS Neurosci Ther, 2024, 30(8): e14836. DOI: 10.1111/cns.14836 .
[72]	蔡湘玉, 梁晓晖, 龚怡婷, 等. 中药活性成分防治缺血性脑卒中机制研究进展[J]. 中草药, 2025, 56(7): 2593-2603. DOI: 10.7501/j.issn.0253-2670.2025.07.032 .
	CAI X Y, LIANG X H, GONG Y T, et al. Research progress on traditional Chinese medicine active ingredient in preventing and treating ischemic stroke[J]. Chin Tradit Herb Drugs, 2025, 56(7): 2593-2603. DOI: 10.7501/j.issn.0253-2670.2025.07.032 .
[73]	杨皓博, 周铭晗, 范文涛. 基于中西医临床病证特点的缺血性中风动物模型评价分析[J]. 中药药理与临床, 2025, 41(3): 96-102. DOI: 10.13412/j.cnki.zyyl.20240423.002 .
	YANG H B, ZHOU M H, FAN W T. Evaluation and analysis of ischemic stroke animal models based on clinical characteristics of traditional Chinese and western medicine[J]. Pharmacol Clin Chin Mater Med, 2025, 41(3): 96-102. DOI: 10.13412/j.cnki.zyyl.20240423.002 .
[74]	温馨如, 林国辉, 宋建勋. 磁共振血管壁成像评估大脑中动脉粥样硬化斑块与复发性卒中相关性研究[J]. 磁共振成像, 2025, 16(4): 25-32. DOI: 10.12015/issn.1674-8034.2025.04.005 .
	WEN X R, LIN G H, SONG J X. Correlation study of atherosclerotic plaques in the middle cerebral artery with recurrent stroke assessed by magnetic resonance vascular wall imaging[J]. Chin J Magn Reson Imag, 2025, 16(4): 25-32. DOI: 10.12015/issn.1674-8034.2025.04.005 .
[75]	钱成, 汪涛, 李英豪, 等. 凋亡小分子探针在急性大脑中动脉栓塞和再通模型中的应用[J]. 中国医学影像学杂志, 2024, 32(10): 977-981, 987. DOI: 10.3969/j.issn.1005-5185.2024.10.001 .
	QIAN C, WANG T, LI Y H, et al. Application of apoptosis small-molecule probe in acute middle cerebral artery embolization and recanalization model[J]. Chin J Med Imag, 2024, 32(10): 977-981, 987. DOI: 10.3969/j.issn.1005-5185.2024.10.001 .
[76]	王尧, 陈心智. 益脑复健方通过调节HIF-1a/BNIP3信号通路对缺血性脑卒中大鼠神经功能损伤的影响[J]. 特产研究:1-1110. DOI: 10.16720/j.cnki.tcyj.2024.099 .
	WANG Y, CHEN X Z. Effects of yinao fujian formula on neurological impairment in ischemic stroke rats by regulating the HIF-1α/BNIP3 signaling pathway[J]. Special Wild Econ Anim Plant Res:1-11. DOI: 10.16720/j.cnki.tcyj.2024.099 .

物种 Species	优点 Advantages	主要品种/品系 Main breeds/strains	主要局限 Main limitations	典型应用场景 Typical application scenarios	常用建模方法 Common modeling methods
大鼠 Rat	手术稳定性高，行为学丰富，适用于药效评价	SD、Wistar、Long-Evans等	基因工具有限	神经保护剂验证、康复训练机制研究	线栓法、光化学法、三氯化铁法、胶原酶法、血管穿刺法、血栓法、双侧颈总动脉结扎
小鼠 Mouse	遗传操作便捷，成本低，适合高通量筛选	C57BL/6（常用）、SV129、BALB/c等，以及各类基因修饰品系	梗死体积变异大、血管脆弱	基因-表型关联、免疫机制研究	线栓法、光化学法、三氯化铁法
非人灵长类 Non-human primate	脑结构/功能高度类人，影像兼容性强	食蟹猴、普通猕猴、狨猴等	实验成本极高、实验动物福利伦理复杂	高级认知障碍研究、临床前终效验证	线栓法及其他定制化手术方案
小型猪 Miniature pig	脑体积大，手术操作方便	哥廷根小型猪、尤卡坦小型猪、巴马香猪、五指山小型猪等	侧支循环异常、康复过程不典型	外科技术开发、急性期介入治疗评价	线栓法、球囊闭塞法、微导管栓塞法
兔 Rabbit	血管介入友好，血栓模型稳定	新西兰大白兔、日本大耳白兔等	缺乏相应的神经行为评价体系	取栓/溶栓器械测试、血栓病理研究	三氯化铁敷贴法、血栓栓塞法
斑马鱼 Zebrafish	活体血管可视化，基因筛选高效	AB系、TU系、TL系等野生型及各类转基因荧光品系	缺乏高级脑结构和认知功能	血管完整性机制、高通量药物初筛	光化学血栓法

物种 Species	优点 Advantages	主要品种/品系 Main breeds/strains	主要局限 Main limitations	典型应用场景 Typical application scenarios	常用建模方法 Common modeling methods
大鼠 Rat	手术稳定性高，行为学丰富，适用于药效评价	SD、Wistar、Long-Evans等	基因工具有限	神经保护剂验证、康复训练机制研究	线栓法、光化学法、三氯化铁法、胶原酶法、血管穿刺法、血栓法、双侧颈总动脉结扎
小鼠 Mouse	遗传操作便捷，成本低，适合高通量筛选	C57BL/6（常用）、SV129、BALB/c等，以及各类基因修饰品系	梗死体积变异大、血管脆弱	基因-表型关联、免疫机制研究	线栓法、光化学法、三氯化铁法
非人灵长类 Non-human primate	脑结构/功能高度类人，影像兼容性强	食蟹猴、普通猕猴、狨猴等	实验成本极高、实验动物福利伦理复杂	高级认知障碍研究、临床前终效验证	线栓法及其他定制化手术方案
小型猪 Miniature pig	脑体积大，手术操作方便	哥廷根小型猪、尤卡坦小型猪、巴马香猪、五指山小型猪等	侧支循环异常、康复过程不典型	外科技术开发、急性期介入治疗评价	线栓法、球囊闭塞法、微导管栓塞法
兔 Rabbit	血管介入友好，血栓模型稳定	新西兰大白兔、日本大耳白兔等	缺乏相应的神经行为评价体系	取栓/溶栓器械测试、血栓病理研究	三氯化铁敷贴法、血栓栓塞法
斑马鱼 Zebrafish	活体血管可视化，基因筛选高效	AB系、TU系、TL系等野生型及各类转基因荧光品系	缺乏高级脑结构和认知功能	血管完整性机制、高通量药物初筛	光化学血栓法

特征 Features	颈外动脉入路 External carotid artery approach	颈总动脉入路 Common carotid artery approach
操作步骤 Procedures	需永久结扎颈外动脉远心端	无需结扎颈外动脉，操作更简便
插入路径 Insertion path	经颈外动脉切口转向颈内动脉	经颈总动脉直接进入颈内动脉
优点 Advantages	插入角度自然，通向颈内动脉的路径直接，成功率较高	保留颈外动脉完整性，对手术创伤更小
缺点 Disadvantages	永久结扎颈外动脉，终止其供血区域血流	易误伤血管内膜或误入颈总动脉近心端
适用场景 Applicable scenarios	无需保留颈外动脉血供的研究	需要保留颈外动脉血流的实验设计

特征 Features	颈外动脉入路 External carotid artery approach	颈总动脉入路 Common carotid artery approach
操作步骤 Procedures	需永久结扎颈外动脉远心端	无需结扎颈外动脉，操作更简便
插入路径 Insertion path	经颈外动脉切口转向颈内动脉	经颈总动脉直接进入颈内动脉
优点 Advantages	插入角度自然，通向颈内动脉的路径直接，成功率较高	保留颈外动脉完整性，对手术创伤更小
缺点 Disadvantages	永久结扎颈外动脉，终止其供血区域血流	易误伤血管内膜或误入颈总动脉近心端
适用场景 Applicable scenarios	无需保留颈外动脉血供的研究	需要保留颈外动脉血流的实验设计

模型方法 Modeling approaches	主要品种/品系 Main breeds/strains	造模原理 Modeling Principles	开颅 Cranio-tomy	优势 Advantages	局限性 Limitations	应用场景 Scope of application
线栓法 Intraluminal filament occlusion model	C57BL/6小鼠、SD雄性大鼠等	插入尼龙线阻断大脑中动脉血流	否	高度可复制性，模拟再灌注损伤	体重要求严格，脑卒中梗死体积难以控制	缺血性脑卒中的再灌注损伤机制、神经保护策略及康复治疗效果
光化学栓塞法 Photothrombotic model	C57BL/6小鼠、SD大鼠等	静脉注射光敏染料，用特定波长进行激活	是	高存活率、定点精准损伤	参数敏感，易自发恢复	缺血性脑卒中的病理机制、药物筛选及治疗方案评估
血栓法 Thromboembolic model	SD大鼠等	直接注射血栓物质	否	高精度，真实性强	技术要求较高，个体差异大	血栓形成机制、抗凝药物疗效及血栓溶解疗法
三氯化铁敷贴法 Topical FeCl₃-induced model	C57BL/6小鼠、SD大鼠等	三氯化铁诱导血管壁化学损伤，形成原位血栓	是	病理生理相关性高，血栓形成过程接近临床	手术创伤大，难以实现再灌注	抗血小板/抗凝药物评价、血栓形成机制研究
双侧颈总动脉结扎法 Bilateral common carotid artery ligation model	SD大鼠等	结扎双侧颈总动脉	否	简单易行，成本低廉	无法完全模拟人类复杂性	血管损伤后的修复机制及新型血管支架材料的生物相容性
自体血注射法 Autologous blood injection model	C57BL/6小鼠、SD大鼠等	立体定位注射自体动脉血形成血肿	是	出血量精确可控、形态一致性好	需立体定位与显微操作，技术要求高	血肿清除策略、颅内压变化、神经炎症及神经保护治疗研究
胶原酶诱导法 Collagenase-induced model	SD大鼠等	胶原酶可降解血管壁中的胶原纤维，破坏血管壁的完整性	是	操作简便，出血量稳定	与自然出血存在差异	出血性脑卒中的发病机制、止血药物及神经保护剂的效果
血管穿刺法 Vessel puncture-induced intracerebral hemorrhage model	SD大鼠等	直接刺入目标血管	是	接近人类病理特征	技术要求高，手术风险大	出血性脑卒中的发病机制、止血药物及神经保护剂的效果

脑卒中动物模型构建与评价方法评述

A Review of Methods for Establishing and Evaluating Animal Models of Stroke

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基因 Genes	人类关联 Human relevance	在脑卒中模型中的作用机制 Mechanisms of action in stroke models
APOE4	阿尔茨海默病和脑卒中的高风险因子	削弱血脑屏障功能，加重脑水肿；损害脑血管自我调节能力；促进β-淀粉样蛋白沉积和脑血管病变，影响脑血流储备；加剧神经炎症和阻碍神经修复
NOTCH3	可导致皮质下梗死伴白质脑病的常染色体显性遗传性脑动脉病	在转基因小鼠Tg（NOTCH3 R169C）中过表达突变基因，会导致血管平滑肌细胞变性、白质损伤和血脑屏障破坏。此类小鼠对脑缺血极度敏感，即使轻微的缺血刺激也能造成严重梗死
HTRA1	可导致皮质下梗死伴白质脑病的常染色体隐性遗传性脑动脉病	突变可导致TGF-β信号通路异常，引起血管平滑肌细胞凋亡和小血管病变
COL4A1和COL4A2	可导致多种脑血管疾病，包括脑出血卒中和缺血性卒中	该基因编码的Ⅳ型胶原蛋白是血管基底膜的关键成分，其突变可破坏血管结构的完整性，导致血管脆性增加，从而在高血压或缺血刺激下更容易发生破裂或闭塞

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