不同免疫抑制状态小鼠鲍曼不动杆菌的致病性差异研究  

The pathogenesis of Acinetobacter baumannii in mice under different immune conditions

作　　者：赵旭[1] 肖舒心 郭蓓宁[1] 

机构地区：[1]复旦大学附属华山医院抗生素研究所,卫生部抗生素临床药理重点实验室,上海200040

出　　处：《中国感染与化疗杂志》2015年第2期155-162,共8页Chinese Journal of Infection and Chemotherapy

基　　金：上海市科委实验动物研究专项基金(12140903203)

摘　　要：目的构建正常小鼠、轻度和重度免疫抑制小鼠鲍曼不动杆菌肺炎模型,研究不同免疫状态下鲍曼不动杆菌的致病性。方法 1分别构建正常小鼠、轻度和重度免疫抑制小鼠鲍曼不动杆菌肺炎模型;2144只ICR雌性小鼠随机分为6组,分别为正常对照组（组1）、轻度免疫抑制组（组2）、重度免疫抑制组（组3）、感染组（组4）、轻度免疫抑制感染组（组5）及重度免疫抑制感染组（组6）,每组24只小鼠。气管插管后组1、组2、组3经气管插管注射生理盐水10μL,组4、组5、组6注射鲍曼不动杆菌菌液（3.8×108 CFU/mL）10μL;3分别于0、24、48、72、120和168 h 6个时间点每组随机选取4只小鼠,进行血白细胞和中性粒细胞计数、小鼠肺组织细菌计数,以及肺组织病理检查。结果组6有5只小鼠死亡,病死率达到20.8%,余组无死亡。组4为免疫功能正常小鼠,感染鲍曼不动杆菌后2 d肺内细菌全部被清除,白细胞及中性粒细胞计数在感染后1~3 d明显上升,5~7 d后基本恢复正常水平,病理示一过性肺组织损伤包括局部肉芽肿形成及肺间质损伤;组6为重度免疫缺陷小鼠,在感染后肺组织中的细菌量持续增长,第3天上升至感染初期的145倍,之后菌量减少。感染2 d内白细胞及中性粒细胞始终处于极低水平,3 d后逐渐恢复至正常水平,至第7天明显升高至正常水平的2倍以上,组织病理示感染7 d后整叶肺呈实变、坏死,肺泡、支气管及血管结构均被破坏;组5与正常小鼠感染过程类似,细菌在第3天被完全清除。结论正常小鼠感染鲍曼不动杆菌后,肺内细菌可以完全清除,但仍有一过性肺组织病理损伤;重度免疫抑制小鼠感染后细菌会在肺内增殖,肺组织病理损伤随时间延长明显加重;机体不同免疫状态可影响鲍曼不动杆菌感染的发展和转归。Objective To establish Acinetobacter baumannii pneumonia models in normal,mild immunodeficient and serious immunodeficient mice,and to examine the pathogenesis of A.baumannii under different immune conditions.Methods A.baumannii pneumonia models were established in normal, mild immunodeficient and serious immunodeficient mice,respectively.One hundred and forty-four mice were randomized into 6 groups including control（group 1）, mild immunosuppression（group 2）,serious immunosuppression（group 3）,infection（group 4）,infected after mild immunosuppression（group 5）and,infected after serious immunosuppression（group 6）,24 mice in each group.After intubation,the mice in group 1,2 and 3 were given sterile saline,while those in groups 4,5,6 were inoculated with10μL of fresh A.baumannii suspension（3.8 × 108 CFU/mL）.Four mice were sacrificed at 0h,24 h,48 h,72 h,120 h and 168 h,respectively in each group.Then blood sample and lung tissue were taken from each mouse aseptically for testing white blood cell（WBC）and neutrophils count,quantitative culture and histopathological analysis.Results Five（20.8%）mice were dead in group 6,while no mouse was dead in other 5 groups.After inoculation of A.baumannii suspension in group4（normal）mice,pulmonary bacterial burden was eliminated over two days.The WBC and neutrophils count were obviously elevated over 1-3 days after infection,and returned to normal over 5-7 days.The histopathologic examination showed transient local granulomas and pulmonary interstitial injury.In group 6,the bacteria multiplied continuously in lungs of serious immunosuppressive mice,increased 145 times over 3 days and then decreased.The total WBC and neutrophils count were extremely low within first 2days,increased since day 3,and continuously increased up to 2 times of the normal level on day 7.The histopathologic changes showed lung consolidation,necrosis and destruction of alveolus,bronchus and blood vessels.The infection process of mild immunosuppression mice（group 5）wa

关 键 词：鲍曼不动杆菌 小鼠肺炎模型 免疫抑制 致病性 

分 类 号：R563.1[医药卫生—呼吸系统] R-332[医药卫生—内科学]