炭疽PasteurⅡ株芽孢气溶胶感染小鼠模型的构建与评价  

Establishment and evaluation of mouse model of Bacillus anthracis Pasteur Ⅱ strain infection via aerosolized intratracheal inoculation

作　　者：翟丽娜 宋晓琳 张丽丽 杨文慧 周冬生 房彤宇 吕蒙 ZHAI Lina;SONG Xiaolin;ZHANG Lili;YANG Wenhui;ZHOU Dongsheng;FANG Tongyu;LYU Meng(State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China;College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029)

机构地区：[1]军事科学院军事医学研究院微生物流行病研究所病原微生物生物安全国家重点实验室,北京100071 [2]北京化工大学生命科学与技术学院,北京100029

出　　处：《中国比较医学杂志》2023年第5期69-76,共8页Chinese Journal of Comparative Medicine

摘　　要：目的构建炭疽PasteurⅡ株芽孢气溶胶感染小鼠模型并评价构建效果。方法选取补体成分C5缺乏的B10.D2-Hc^(0)H2^(d)H2-T18c/oSnJ小鼠,以气溶胶肺递送途径感染炭疽PasteurⅡ株芽孢(减毒株),研究感染后的疾病进展、细菌载量、组织病理学改变、细胞因子和急性反应蛋白水平。结果小鼠半数致死剂量为5×10^(3)CFU。炭疽芽孢肺部感染小鼠12 h后就出现多器官转移并引发菌血症;组织病理改变及炎症反应与其他物种(包括兔、非人灵长类及人类)相似;血清和肺泡灌洗液中的C反应蛋白和血清淀粉样蛋白P水平表明小鼠感染后可激发急性炎症反应。结论该模型可作为替代性的小动物模型,用于进一步阐明炭疽芽孢杆菌的发病机制和宿主对炭疽芽孢易感性的差异,为炭疽疫苗和治疗药物提供新方法。Objective To establish and evaluate a mouse model of inhaled anthrax infection by Bacillus anthracis(Pasteur Ⅱ strain)spores by aerosolized intratracheal inoculation.Methods B10.D2⁃Hc^(0)H2^(d) H2⁃T18c/oSnJ mice lacking complement component C5 were infected with Bacillus anthracis Pasteur II strain spores(attenuated strain)by aerosolized intratracheal inoculation.Disease progression,tissue bacterial load,histopathological changes,cytokine response,and acute reactive protein levels were examined after infection.Results The median lethal dose was 5×10^(3)CFU.Multiple organ metastasis and bacteremia occurred within 12 hours after pulmonary infection of anthrax spores.Histopathological changes and inflammatory responses were similar to those in other species including rabbits,nonhuman primates,and humans.C⁃reactive protein and amyloid protein P levels in serum and alveolar lavage fluid indicated that acute inflammatory responses were triggered after infection.Conclusions This model can be used as an alternative small animal model to further elucidate the pathogenesis of Bacillus anthracis and differences in host susceptibility to B.anthracis,providing new approaches for anthrax vaccines and therapeutic drug development.

关 键 词：炭疽芽孢杆菌 小鼠模型 气溶胶 吸入性炭疽 

分 类 号：R-33[医药卫生]