噬菌体对鲍曼不动杆菌所致小鼠肠源性脓毒症的治疗效果  

Bacteriophage therapy for gut-derived sepsis caused by Acinetobacter baumannii in mice

作　　者：李菁华[1] 余静丹[2] 史红艳[1] 王丹 逯茵茵[1] 张哲[1] 孙延波[1] 

机构地区：[1]吉林大学白求恩医学部基础医学院病原生物学系,长春130021 [2]湖北省十堰市东风公司总医院检验科 [3]长春金赛药业有限责任公司

出　　处：《中华临床感染病杂志》2014年第3期197-201,共5页Chinese Journal of Clinical Infectious Diseases

基　　金：国家自然科学基金委主任项目（81150037）

摘　　要：目的 观察噬菌体对鲍曼不动杆菌引起的小鼠肠源性脓毒症的治疗效果.方法 采用双层琼脂法从环境中分离鲍曼不动杆菌噬菌体.通过腹腔注射氨苄青霉素和环磷酰胺的方法,同时经口感染耐氨苄青霉素鲍曼不动杆菌,建立小鼠肠源性脓毒症模型.在细菌感染前1d、感染结束后2d,以及感染结束后6d给予噬菌体治疗,观察小鼠的存活情况.另取未给予噬菌体治疗小鼠作为对照.各组分别设6只小鼠.采用成组设计的两样本均数t检验比较噬菌体治疗组和对照组小鼠外周血和肝脏内炎症因子水平,以及肝脏和脾脏内的细菌数量.结果 鲍曼不动杆菌引起肠源性脓毒症小鼠全部死亡的最小致死量为1×107 CFU/mL.在感染前、结束后2d和6 d给予噬菌体治疗,分别有2,4,3只小鼠存活,对照组全部死亡.噬菌体治疗组小鼠外周血白细胞介素（IL）-1β、肿瘤坏子因子（TNF）-α和IL-6水平分别为（105±6） ng/L,（105±11）ng/L和（104±12） ng/L,明显低于对照组（t=5.04,9.05和9.33,P＜0.01）;噬菌体治疗组小鼠肝脏内的IL-1 β和TNF-α水平分别为（104 ±9） ng/L和（104±11）ng/L,亦低于对照组（t=13.70和12.80,P＜0.01）,但IL-6水平治疗组与对照组比较差异无统计学意义（t=1.06,P＞0.05）;噬菌体治疗组小鼠肝脏和脾脏内细菌数量分别为（2.9±1.3）×103CFU/g和（8.3±7.6）×102 CFU/g,明显低于对照组（=9.16和8.96,P＜0.01）.结论 噬菌体治疗鲍曼不动杆菌引起的肠源性脓毒症确切有效.Objective To evaluate bacteriophage therapy for gut-derived sepsis caused by Acinetobacter baumannii in mice.Methods Lyric phages of Acinetobacter baumannii were isolated from environment by using double-layer agar method.A murine model of gut-derived sepsis was established by oral administration of ampicillin-resistant Acinetobacter baumannii and injection of ampicillin and cyclophosphamide into peritoneal cavities of mice.Bacteriophage therapy were given 1 d before infection （group 1）,2 d（group 2） and 6 d（group 3） after infection.The survival of the mice was observed,mice without bacteriophage therapy were as control.Independent-sample t test was performed to compare inflammatory cytokines levels in peripheral blood and liver,number of bacteria in liver and spleen between mice with and without bacteriophage therapy.Results The minimal lethal dose of Acinetobacter baumannii for mice with gut-derived sepsis was 1 × 107 CFU/mL.The survival of the mice in group 2 （4/6 survived）,which were treated with bacteriophage 2 d after inoculation of Acinetobacter baumannii,was higher than those of group 1 （2/6 survived）,group 3 （3/6 survived） and the control group （phage-untreated,0/6 survived）.Interleukin （IL）-1 β,tumor necrosis factor （TNF）-α and IL-6 in peripheral blood in mice with bacteriophage therapy were （105 ±6） ng/L,（105 ± 11） ng/L and （104 ± 12）ng/L,which were lower than those in control group （t =5.04,9.05 and 9.33,P 〈 0.01） ; IL-1 β and TNF-α in liver of mice with bacteriophage therapy were （104 ± 9） ng/L and （104 ± 11） ng/L,which were lower than those in the controls （t =13.70 and 12.80,P 〈0.01）,but IL-6 levels were not of statistical difference between therapy and control groups （t =1.06,P 〉 0.05）.Number of bacteria in liver and spleen in mice with bacteriophage therapy were （2.9 ± 1.3） × 103CFU/g and （8.3 ±7.6） × 102 CFU/g,which were also lower than those in control group （t =9.16 and 8.96,P 〈 0.01）.Conclusio

关 键 词：细菌噬菌体 鲍氏不动杆菌 脓毒症 

分 类 号：R446.5[医药卫生—诊断学]