血友病性关节炎动物模型的研究进展  

Progress in animal models of hemophilic arthritis

作　　者：林锟 何宪顺 田佳庆 陆舜 何敏聪 林天烨 何晓铭 范帅 杨宏光 于天启 张大光[6] 何伟 魏秋实 LIN Kun;HE Xianshun;TIAN Jiaqing;LU Shun;HE Mincong;LIN Tianye;HE Xiaoming;FAN Shuai;YANG Hongguang;YU Tianqi;ZHANG Daguang;HE Wei;WEI Qiushi(the Third Clinical School of Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Joint Center,the Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510378,China;Guangdong Institute of Chinese Medicine and Orthopedics,Guangzhou 510378,China;Department of Osteoporosis,the Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510378,China;Regional TCM Hematology Treatment Center,the Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510378,China;the First Hospital of Jilin University,Changchun 130061,China)

机构地区：[1]广州中医药大学第三临床医学院,广州510006 [2]广州中医药大学第三附属医院关节中心,广州510378 [3]广东省中医骨伤研究院,广州510378 [4]广州中医药大学第三附属医院骨质疏松科,广州510378 [5]广州中医药大学第三附属医院区域中医血液病诊疗中心,广州510378 [6]吉林大学第一医院,长春130061

出　　处：《中国实验动物学报》2024年第4期523-529,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金面上项目(82274544,81873327);国家自然科学基金青年科学基金(82004392);2022年度“揭榜挂帅”项目(毕科合重大专项[2022] 1号);“双一流”与高水平大学学科协同创新团队重大项目(2021XK05);“双一流”与高水平大学学科协同创新团队培育项目(2021XK41);开放课题重点项目(GYH202101-01,GYH202101-04);国家中医优势专科建设项目(440000220000000043009)。

摘　　要：血友病的反复出血并发血友病性关节炎(hemophilia arthritis, HA),严重影响患者生活,消耗大量社会医疗资源,受限于伦理要求,需要建立HA动物模型进行研究。为了总结血友病性关节炎动物模型的研究进展,本文查阅近年国内外有关动物HA模型的研究文献,从物种选择、建模方法以及组织病理学、影像学评价方法等方面进行综述。物种选择上包括啮齿类鼠类、新西兰兔、比格犬、小型猪、食蟹猴等;造模方法包括基因敲除创伤模型、基因敲除自发模型和注射模型,其中基因敲除自发模型最接近人类HA的自发出血并发关节炎的病理生理过程,更贴近人类HA,但是由于造模成本高、表型不稳定、成活率低等因素,该模型并不作为动物实验研究的首选;相比之下,基因敲除创伤模型具有造模时间短、稳定性强、成功率高等特点,因此被广泛应用。HA模型的评价除了多种大体评分方法外,还包括MRI、micro-CT、MSKUS/PD等多种影像学方法可供选择。通过对HA模型研究进展的综述,为研究其发病机制和疗效验证提供更多依据,弥补HA临床数据的匮乏,特别是中医药治疗方面。Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

关 键 词：血友病性关节炎 动物模型 评价方法 组织病理学 影像学 

分 类 号：Q95-33[生物学—动物学]