免疫介导再生障碍性贫血小鼠模型制备条件的实验比较研究  

Experimental comparative study on preparation conditions of immune-mediated aplastic anemia mouse model

作　　者：张梓倩[1] 李姝仪 袁继巧 杨慧[1] 范燕楠 白金叶[1] 马培[1] 林明宝[1] 侯琦[1] ZHANG Zi-qian;LI Shu-yi;YUAN Ji-qiao;YANG Hui;FAN Yan-nan;BAI Jin-ye;MA Pei;LIN Ming-bao;HOU Qi(Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《中国药理学通报》2020年第8期1178-1183,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金项目(No 81803810);北京协和医学院“中央高校基本科研业务费”专项资金项目(No 3332018091);医科院创新工程项目(No 2016-I2M-2-006);新药创制重大专项(No 2018ZX09711001-003-001,2018ZX09711001-001-001)。

摘　　要：目的对比研究影响小鼠再生障碍性贫血(aplastic anemia,AA)模型造模过程的主要因素,优化模型条件。方法采用钴-60γ射线照射联合免疫细胞静脉注射,建立免疫介导的小鼠AA模型,以外周血全血细胞分类计数和网织红细胞比例为检测指标,对造模影响因素进行考察;并以AA临床治疗药物环孢素验证模型可靠性。结果射线照射剂量、动物性别、注射免疫细胞类别、指标检测时间点均是影响造模程度与数据质量的重要因素,根据本研究,最优模型条件为♂小鼠5.80 Gy钴-60γ射线照射联合胸腺-脾细胞2∶1静脉注射,造模后第二周进行指标检测。结论本研究有利于实验人员在AA药理学研究中对实验过程进行更为有效的控制、保证数据质量,为AA治疗药物筛选评价与机制研究的高效进行提供保障。Aim To compare the main factors affecting the modeling process of aplastic anemia(AA)mouse model and to optimize the modeling conditions.Methods An immune-mediated AA mouse model was established by cobalt-60γ-irradiation combined with intravenous injection of immune cells,the factors influencing modeling were examined by peripheral blood cell counts and the proportion of reticulocytes,and the reliability of the model was validated by cyclosporine,a clinical drug for the treatment of AA.Results The dose of radiation,the sex of animal,the type of injected immune cells,and the time for indicator detection were all important factors affecting the severity degree of the model and data quality.According to the study,the optimal modeling conditions were 5.8 Gy of cobalt-60γ-irradiation followed by intravenous injection of mixed thymus-spleen cells(2∶1)on♂mice and indicator detection should be carried out two weeks after modeling.Conclusions This study will be helpful for experimental staff to control the experimental process of pharmacological research in the field of AA more effectively and to ensure the quality of the experimental data,which is an assurance for efficient anti-AA drugs screening,evaluation and mechanism research.

关 键 词：再生障碍性贫血 模型 小鼠 雌雄差异 全血细胞 网织红细胞 

分 类 号：R-332[医药卫生] R322.21