噬菌体对小鼠肠源性铜绿假单胞菌感染的治疗作用

目的：探讨铜绿假单胞菌噬菌体对小鼠肠源性铜绿假单胞菌感染的治疗作用,以阐明噬菌体潜在的应用价值。 方法：利用噬斑法从居民生活污水中分离和鉴定铜绿假单胞菌噬菌体,用氨苄青霉素造成小鼠肠道菌群失调同时注射环磷酰胺使小鼠免疫功能下降，通过口服铜绿假单胞菌建立动物感染模型。将动物分为治疗组Ⅰ(在 感染前1 d给予噬菌体)、治疗组Ⅱ(在感染的第5天给予噬菌体)、治疗组Ⅲ(在感染的第10天给予噬菌体)和对照组(不给予噬菌体)，观察噬菌体的抗感染疗效。结果：采用噬斑法分离和纯化4株铜绿假单胞菌噬菌体。电镜显示噬菌体头部呈立体对称，有一短尾。在肠源性铜绿假单胞菌感染的动物模型中,小鼠的死亡率为100%。 治疗组Ⅰ小鼠存活率为70%， 与对照组比较差异有显著性(P<0.01)。治疗组Ⅱ小鼠存活率为80%，与对照组比较差异亦有显著性(P<0.01)。在感染的第10天给予噬菌体治疗，小鼠存活率降至10%，与对照组比较差异无显著性(P>0.05)。结论：早期应用噬菌体对铜绿假单胞菌引起的肠源性感染有明显的治疗作用，提示噬菌体可以作为一种新型的抗感染生物制剂。

Therapeutic effect of bacteriophage on intestine-derived infection caused by Pseudomonas aeruginosa in mice

Objective To explore the application of bacteriophage therapy against intestine-derived infection caused by Pseudomonas aeruginosa and to evaluate the potential value of bacteriophages.Methods Phages were isolated and purified by conventional processes.A murine model of intestine-derived infection caused by Pseudomonas aeruginosa was established through administration of ampicillin and cyclophosphamide(CY) by intraperitoneal injection.Animals were divided into treatment group Ⅰ(phage administration,1 d before the bacterial challenge),treatment group Ⅱ(phage administration,5 d after the bacterial challenge),treatment group Ⅲ(phage administration,10 d after the bacterial challenge) and control group(no phage administration) to evaluate anti-infection efficacy of phage.Results Four strains of lytic phage were isolated from sewage.1 d before the bacteria challenge,oral administration of lytic phages was sufficiently to rescue 70% of the animals compared with control animals(P<0.01).5 d after the bacteria challenge,oral administration of lytic phages was significantly to rescue 80% of the animals compared with control animals(P<0.01).However,10 d after the bacteria challenge,oral administration of lytic phages was only to rescue 10% of the animals(P>0.05).Conclusion The phage treatment significantly improve the survival rate of mice during the early stage of infection;it suggestes that the phages may serve as an effective agent against bacterial infection.