模式生物斑马鱼在卒中研究中的应用

doi:10.3969/j.issn.1673-5765.2022.05.019

摘要/Abstract

摘要： 动物模型为探索脑血管疾病的病理生理演变及药物研发提供了必要工具。斑马鱼（zebrafish，Danio rerio）是一种理想的脊椎模式生物，具有体型小、繁殖能力强、可视性好、实验周期短、成本低、遗传序列与人类高度相近等特点，在活体血管研究方面具备自身独特的优势，已被越来越多地应用于卒中相关的研究当中。本文概括介绍了斑马鱼模型的特点及其在卒中研究中的应用现状，以期为后续的研究提供一定的帮助。

文章导读： 本文通过总结归纳斑马鱼相对于传统模式生物在体型、繁殖能力、成本上的优势，以及血管可视性佳、遗传序列与人类高度相近、药物筛选便捷等特点,为卒中领域研究者在模型构建与模式生物的选用上提供了参考。

关键词: 斑马鱼; 模式生物; 脑血管疾病; 卒中

Abstract: Animal model provides a necessary tool for exploring the complex pathophysiological process of cerebrovascular disease and drug development. Zebrafish (Danio rerio) is an ideal spinal model organism, which has the characteristics of small size, strong reproductive capacity, good visibility, short experimental period, and low cost. In addition, the genetic sequence of zebrafish is highly similar to human. It has its own unique advantages in living vascular research, and has been more and more used in stroke research. This paper introduced the characteristics of zebrafish model and its application in stroke research, to provide some help for the follow-up research.

Key words: Zebrafish; Model organism; Cerebrovascular disease; Stroke

莫东灿, 刘柳余, 李肖玲, 李建立, 罗曼. 模式生物斑马鱼在卒中研究中的应用[J]. 中国卒中杂志, 2022, 17(05): 548-552.

MO Dongcan, LIU Liuyu, LI Xiaoling, LI Jianli, LUO Man. Application of Zebrafish Model Organism in Stroke Research[J]. Chinese Journal of Stroke, 2022, 17(05): 548-552.

参考文献

[1] WANG W Z，JIANG B，SUN H X，et al. Prevalence，incidence，and mortality of stroke in China：results from a nationwide population-based survey of 480 687 adults[J]. Circulation，2017，135（8）：759-771.
[2] ISOGAI S，HORIGUCHI M，WEINSTEIN B M.The vascular anatomy of the developing zebrafish：an atlas of embryonic and early larval development[J].Dev Biol，2001，230（2）：278-301.
[3] QUIÑONEZ-SILVERO C，HÜBNER K，HERZOG W. Development of the brain vasculature and the blood-brain barrier in zebrafish[J]. Dev Biol，2020，457（2）：181-190.
[4] FUJITA M，CHA Y R，PHAM V N，et al. Assembly and patterning of the vascular network of the vertebrate hindbrain[J]. Development，2011，138（9）：1705-1715.
[5] HOWE K，CLARK M D，TORROJA C F，et al. The zebrafish reference genome sequence and its relationship to the human genome[J]. Nature，2013，496（7446）：498-503.
[6] KETTLEBOROUGH R N W，BUSCH-NENTWICH E M，HARVEY S A，et al. A systematic genomewide analysis of zebrafish protein-coding gene function[J]. Nature，2013，496（7446）：494-497.
[7] JIN S W，BEIS D，MITCHELL T，et al. Cellular and molecular analyses of vascular tube and lumen formation in zebrafish[J]. Development，2005，132（23）：5199-5209.
[8] O'BROWN N M，PFAU S J，GU C，et al. Bridging barriers：a comparative look at the blood-brain barrier across organisms[J]. Genes Dev，2018，32（7/8）：466-478.
[9] ZHANG H Q，WALDMANN L，MANUEL R，et al. zOPT：an open source optical projection tomography system and methods for rapid 3D zebraf ish imaging[J]. Biomed Opt Express，2020，11（8）：4290-4305.
[10] HOGAN B M，SCHULTE-MERKER S. How to plumb a pisces：understanding vascular development and disease using zebrafish embryos[J]. Dev Cell，2017，42（6）：567-583.
[11] 中华医学会神经病学分会，中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志，2018，51（9）：666-682.
[12] YIN W，CARBALLO-JANE E，MCLAREN D G，et al. Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia[J]. J Lipid Res，2012，53（1）：51-65.
[13] SCHLEGEL A. Zebrafish models for dyslipidemia and atherosclerosis research[J/OL]. Front Endocrinol（Lausanne），2016，7：159[2021-12-08]. https://doi.org/10.3389/fendo.2016.00159.
[14] FANG L，GREEN S R，BAEK J S，et al. In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish[J]. J Clin Invest，2011，121（12）：4861-4869.
[15] GUT P，REISCHAUER S，STAINIER D Y R，et al. Little fish，big data：zebrafish as a model for cardiovascular and metabolic disease[J]. Physiol Rev，2017，97（3）：889-938.
[16] KIM J G，BAE S J，LEE H S，et al. Claudin5a is required for proper inflation of Kupffer's vesicle lumen and organ laterality[J/OL]. PLoS One，2017，12（8）：e0182047[2021-12-08]. https://doi.org/10.1371/journal.pone.0182047.

[17] JEONG J Y，KWON H B，AHN J C，et al .Functional and developmental analysis of the bloodbrain barrier in zebrafish[J]. Brain Res Bull，2008，75（5）：619-628.
[18] HÜBNER K，CABOCHETTE P，DIÉGUEZHURTADO R，et al. Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling[J/OL]. Nat Commun，2018，9（1）：4860[2021-12-08].https://doi.org/10.1038/s41467-018-07302-x.
[19] ZAUCKER A，MERCURIO S，STERNHEIM N，et al. Notch3 is essential for oligodendrocyte development and vascular integrity in zebrafish[J].Dis Model Mech，2013，6（5）：1246-1259.
[20] Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology（CHARGE）Consor tium，the Stroke Genetics Network（SiGN），the International Stroke Genetics Consortium（ISGC）. Identification of additional risk loci for stroke and small vessel disease：a metaanalysis of genome-wide association studies[J].Lancet Neurol，2016，15（7）：695-707.
[21] JIN D Q，ZHU D Q，FANG Y B，et al. Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures[J]. J Genet Genomics，2017，44（10）：483-492.
[22] WANG H C，LUO L F，YANG D Q. Loss of Gspt1l disturbs the patterning of the brain central arteries in zebrafish[J]. Biochem Biophys Res Commun，2017，486（1）：156-162.
[23] WU X，LUO X，ZHU Q Q，et al. The roles of thrombospondins in hemorrhagic stroke[J/OL]. Biomed Res Int，2017，2017：8403184[2021-12-08].https://doi.org/10.1155/2017/8403184.
[24] CRILLY S，NJEGIC A，PARRY-JONES A R，et al. Using zebrafish larvae to study the pathological consequences of hemorrhagic stroke[J]. J Vis Exp，2019（148）[2021-12-08]. https://doi.org/10.3791/59716.
[25] DONNINI S，SOLITO R，CETTI E，et al. Abeta peptides accelerate the senescence of endothelial cells in vitro and in vivo，impairing angiogenesis[J].FASEB J，2010，24（7）：2385-2395.
[26] PARK S O，LEE Y J，SEKI T，et al. ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemor rhag ic telangiectasia type 2[J]. Blood，2008，111（2）：633-642.
[27] YORUK B，GILLERS B S，CHI N C，et al. Ccm3 functions in a manner distinct from Ccm1 and Ccm2 in a zebrafish model of CCM vascular disease[J].Dev Biol，2012，362（2）：121-131.
[28] GORE A V，LAMPUGNANI M G，DYE L，et al. Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke[J]. Dis Model Mech，2008，1（4/5）：275-281.
[29] SANTIAGO-SIM T，FANG X，HENNESSY M L，et al. THSD1（thrombospondin type 1 domain containing protein 1）mutation in the pathogenesis of int racranial aneurysm and subarachnoid hemorrhage[J]. Stroke，2016，47（12）：3005-3013.
[30] ZOU J，LI W Q，LI Q，et al. Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish[J]. Circ Res，2011，108（2）：201-209.
[31] SCHUERMANN A，HELKER C S，HERZOG W. Angiogenesis in zebrafish[J/OL]. Semin Cell Dev Biol，2014，31：106-114[2021-12-08]. https://doi.org/10.1016/j.semcdb.2014.04.037.
[32] ZHU X Y，LIU H C，GUO S Y，et al. A zebrafish thrombosis model for assessing antithrombotic drugs[J]. Zebrafish，2016，13（4）：335-344.
[33] CHEN Y，CHEN P D，BAO B H，et al. Antith rombot ic and pro-angiogenic effect s of Rubia cordifolia extract in zebraf ish[J/OL]. J Ethnopharmacol，2018，219：152-160[2021-12-08]. https://doi.org/10.1016/j.jep.2017.11.005.
[34] PETERSON R T，SHAW S Y，PETERSON T A，et al. Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation[J]. Nat Biotechnol，2004，22（5）：595-599.
[35] 赵崇军，田敬欢，王金凤，等. 斑马鱼在中药研究中的应用进展[J]. 中草药，2015，46（17）：2635-2648.
[36] 方子寒，漆仲文，谢盈彧，等. 中药对斑马鱼血管新生干预作用的研究进展[J]. 中草药，2018，49（14）：3441-3445.
[37] BENCHOULA K，KHATIB A，JAFFAR A，et al.The promise of zebrafish as a model of metabolic syndrome[J]. Exp Anim，2019，68（4）：407-416.