目的观察噬菌体AB3在耐碳青霉烯类鲍氏不动杆菌(CRAB)肺部感染小鼠模型中的疗效、代谢规律、对宿主免疫功能的影响,以及脂质体包被对噬菌体AB3在肺组织内存留时间的影响。方法建立CRAB肺部感染小鼠模型,通过滴鼻、肌内注射及腹腔注射3种途径分别将噬菌体AB3注入小鼠体内,观察其在肺组织内的代谢规律及产生中和抗体的效价,确定最佳给药途径并观察其疗效;通过检测小鼠血清细胞因子的水平,了解噬菌体AB3对宿主免疫功能的影响;通过制备脂质体包被液,进一步延长噬菌体AB3在小鼠肺组织中的存留时间。结果滴鼻途径进入的噬菌体AB3,240 min时仍可测出其滴度,长于另2种给药途径,d 7产生低效价的中和抗体,d 28之后中和抗体效价逐渐下降为0,而另2种给药途径的中和抗体效价从d 7开始逐渐增高;噬菌体AB3滴鼻组小鼠给药5 wk后,血清IFN-γ含量明显高于对照组[(280±33)ng·L~(-1) vs.(224±27)ng·L~(-1),P<0.05];噬菌体AB3治疗组小鼠肺组织结构基本正常,存活率明显高于对照组(90%vs.0,P<0.01);噬菌体AB3脂质体包被液经过滴鼻途径进入小鼠体内,在肺组织中的存留时间可延长至300 min,相比未包被组d 7产生更低效价的中和抗体,d 14后中和抗体效价逐渐下降为0,小鼠存活率明显高于对照组(80%vs.0,P<0.01),而与未包被组存活率相比无显著差异(80%vs.90%,P>0.05)。结论噬菌体AB3不仅可有效治疗CRAB肺部感染,还能增强宿主细胞免疫功能。经鼻途径是最佳的给药途径,脂质体包被液可有效延长噬菌体AB3在肺组织内的存留时间。 OBJECTIVE: To observe the therapeutic effect, metabolism and immune function of bacteriophage AB3 on mouse models of lung infection with carbapenem-resistant Acinetobacter baumannii (CRAB), and the effect of liposome coating on phage AB3 Impact of tissue retention time. Methods A murine model of lung infection by CRAB was established. The phage AB3 was injected into mice by intranasal injection, intramuscular injection and intraperitoneal injection respectively. The metabolism and production of neutralizing antibody in lung tissue were observed. Determine the optimal route of administration and observe its curative effect; Through the detection of serum levels of cytokines in mice to understand the impact of bacteriophage AB3 on host immune function; by the preparation of liposomal coating solution, to further extend the phage AB3 in mouse lung tissue The retention time. Results The titer of phage AB3 was still measurable at 240 min after instillation into the nasal mucosa, which was longer than the other two routes of administration. The low titer of neutralizing antibody was produced on day 7, and the titer of neutralizing antibody decreased gradually after day 28 0, while the neutralizing antibody titers of the other two routes of administration increased gradually from day 7. The phagocytosis levels of IFN-γ in the nasal mice of phagocytosis group were significantly higher than that of the control group ) ng · L -1 (224 ± 27) ng · L -1, P <0.05]. The lung tissue of the phage AB3-treated mice was basically normal and the survival rate was significantly higher than that of the control group 90% vs.0, P <0.01). The phage AB3 liposome coating solution was transfused nasally into the mice and the retention time in the lung tissue could be prolonged to 300 min compared with the non-coated group d 7 The lower titer of neutralizing antibody, the neutralizing antibody titer after d 14 gradually decreased to 0, the survival rate of mice was significantly higher than that of the control group (80% vs.0, P <0.01), but not with the coated group There was no significant difference between the two groups (80% vs.90%, P> 0.05). Conclusion Bacteriophage AB3 can not only effectively treat pulmonary infection of CRAB, but also enhance host cell immune function. Nasal route is the best route of administration, liposome coating liquid can effectively extend the survival time of bacteriophage AB3 in the lung tissue.