肺炎克雷伯杆菌致重症肺炎小鼠模型的建立  

Establishment of a severe pneumonia mouse model induced by Klebsiella pneumoniae

作　　者：程俞梦 江宇航 万冉 程思远 邢小香 赵帅军 赵鹏 李建生[1,2,3] CHENG Yumeng;JIANG Yuhang;WAN Ran;CHENG Siyuan;XING Xiaoxi-ang;ZHAO Shuaijun;ZHAO Peng;LI Jiansheng(Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province&Ministry of Education,Henan Key Laboratory of Chinese Medicine for Respiratory Disease,Henan University of Chinese Medicine,Zhengzhou 450046,China;Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450046,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,河南省中医药防治呼吸病重点实验室,河南郑州450046 [2]河南中医药大学中医药科学院,河南郑州450046 [3]河南中医药大学第一附属医院,河南郑州450000

出　　处：《中国病理生理杂志》2024年第11期2185-2192,共8页Chinese Journal of Pathophysiology

基　　金：2022年度省级科技研发计划联合基金资助项目(No.222301420070);科技创新团队培育项目(No.HSRP-DF⁃CTCM-T-1);2024年度河南省高校科技创新人才支持计划资助项目(No.24HASTIT073)。

摘　　要：目的:建立细菌感染的重症肺炎小鼠模型。方法:将102只雄性SPF级C57BL/6J小鼠随机分为对照组(30只)、模型组(72只),气管滴注5×10^(9) CFU肺炎克雷伯杆菌,于造模后第1、2、4、8、14天处死小鼠,考察小鼠的一般情况、体重及死亡率、白细胞及中性粒细胞数、炎症因子水平、肺及心、肝、脾、肾、肠组织病理等。结果:与对照组比较,模型组小鼠造模后6 h~4 d出现呼吸急促、蜷缩聚集等表现且逐渐加重,体重持续下降,第5~14天上述表现逐渐缓解(P<0.01);模型组小鼠第1~8天动脉血氧饱和度持续下降至80.7%(P<0.01),第9~14天逐渐恢复至正常水平;模型组小鼠第1~9天死亡23只,第10天后无死亡,死亡率达31.9%(P<0.01);模型组小鼠第1~2天肺组织炎症细胞浸润、充血水肿明显,第4~8天仍可见较多炎症细胞浸润与肺泡结构紊乱,第14天可见肺泡破裂融合(P<0.05或P<0.01);模型组小鼠第1~8天外周血中性粒细胞数、白细胞数及肺泡灌洗液蛋白含量、总细胞数、中性粒细胞比例及炎症因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)和IL-6水平均显著升高(P<0.05或P<0.01);模型组小鼠心、肝组织无明显病理改变,脾、肾、肠组织病理改变明显:脾脏红髓与白髓界线不清,肾小球、肾小管及集合管周围间质明显充血、水肿,结肠黏膜层大量炎症细胞浸润。结论:气管滴注5×10^(9) CFU肺炎克雷伯杆菌诱导肺炎模型小鼠表现出重症肺炎的临床病理改变,可以为重症肺炎的发病机制及药物研究提供有效模型。AIM:To establish a severe pneumonia mouse model induced by bacterial infection.METHODS:A total of 102 male SPF C57BL/6J mice were randomly divided into a control group and a model group.Klebsiella pneu-moniae was administered via tracheal instillation at a concentration of 5×10^(9) CFU.Mice were euthanized on days 1,2,4,8,and 14 post-infection to assess general condition,body weight,mortality,white blood cell and neutrophil counts,in-flammatory markers,and pathological changes in lung,heart,liver,spleen,kidney,and intestinal tissues.RESULTS:Mice in the model group exhibited symptoms such as dyspnea and huddling from 6 hours to 4 days post-infection,which progressively worsened,accompanied by continuous weight loss(P<0.01).These symptoms gradually resolved between days 5 and 14.Arterial oxygen saturation in the model group dropped to 80.7%from days 1 to 8(P<0.01)but returned to normal from days 9 to 14.A total of 23 model mice died between days 1 and 9,with no deaths thereafter,resulting in a mortality rate of 31.9%(P<0.01).Pathological examination revealed inflammatory cell infiltration,congestion,and ede-ma in lung tissue from days 1 to 2,with continued inflammatory cell infiltration,alveolar structural disorganization from days 4 to 8,and alveolar rupture and fusion by day 14(P<0.05 or P<0.01).Additionally,model mice showed significant increases in neutrophil count,white blood cell count,protein content in bronchoalveolar lavage fluid,total cell count,neutrophil ratio,and levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in peripheral blood from days 1 to 8(P<0.05 or P<0.01).No significant pathological changes were observed in heart and liver tissues,while spleen,kidney,and intestinal tissues exhibited notable pathological changes:indistinct boundaries be-tween red and white pulp in the spleen,significant congestion and edema around renal glomeruli,renal tubules,and col-lecting ducts,and extensive inflammatory cell infiltration in the colonic mucosa.CONCLUSION:Trac

关 键 词：重症肺炎 动物模型 肺炎克雷伯杆菌 

分 类 号：R563.1[医药卫生—呼吸系统] R332[医药卫生—内科学] Q331[医药卫生—临床医学]