一种改良的小鼠铜绿假单胞菌慢性肺部感染模型的建立与评价OA
Establishment and evaluation of an improved mouse model of chronic pulmonary Pseudomonas aeruginosa infection
目的 建立改良型小鼠铜绿假单胞菌(Pseudomonas aeruginosa,PA)慢性肺部感染模型,并对该模型进行系统评价,为药物治疗PA慢性肺部感染提供一种可靠的模型建立方法.方法 通过一种改良的简便可行的方法制备包被PA的藻酸盐微菌珠,采用气管插管滴注法构建C57BL/6J小鼠PA慢性肺部感染模型.通过观察小鼠生理状态变化,血常规分析,支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)与肺组织载菌量测定、炎症因子表达量测定及组织病理切片分析对模型是否成功进行系统评价并确认.结果 当小鼠经气管内滴注包被PA的藻酸盐微菌珠后,与正常组及0.9%氯化钠溶液藻酸盐微珠组相比,感染组小鼠生理状态不佳,体质量减轻.其肺组织匀浆液及BALF均培养出 PA,且血液中白细胞和中性粒细胞数目显著增多(P<0.05),同时BALF中促炎因子TNF-α及降钙素原(procalcitionly,PCT)含量均显著升高.此外,肺组织病理切片苏木素-伊红(HE)和Masson染色结果也显示模型组小鼠肺组织有明显的炎症细胞浸润及病理改变.结论 本研究通过改良的方法成功制备了包裹PA的藻酸盐微菌珠,将其通过气管插管滴注法接种至小鼠肺部,成功建立了小鼠PA慢性肺部感染动物模型,为PA的药物治疗提供了一种切实可行的实验动物模型.
Objective To establish and systematically evaluate a mouse chronic pulmonary Pseudomonas aeruginosa(PA)infection model,providing a reliable method for establishing a model for drug treatment of chronic PA infections.Methods A feasible modified method was used to prepare PA-coated alginate microbeads.A chronic PA infection model was established in C57BL/6J mice using tracheal intubation instillation.Model success was systematically evaluated by observing changes in physiological state,blood routine analysis,bacterial load measurements in bronchoalveolar lavage fluid(BALF)and lung tissue,measurement of inflammatory cytokine expression,and histopathological section analysis.Results After intratracheal instillation of alginate microbeads coated with PA,the infected mice showed poorer physiological condition and higher mass loss compared with mice in the normal and the saline-alginate microbead groups.PA was cultured from model mouse lung tissue homogenate and BALF,and the number of white cells and neutrophils in the blood significantly increased(P<0.05).Additionally,levels of the pro-inflammatory cytokines tumor necrosis factor-α(TNF-α)and procalcitonin(PCA)in BALF were significantly elevated.Hematoxylin-eosin(HE)and Masson staining of lung tissue pathological sections revealed significant inflammatory cell infiltration and pathological changes in the model group.Conclusions PA-coated alginate microbeads were successfully prepared using a modified method,and a chronic pulmonary PA infection model was established in mice through tracheal intubation instillation,providing a practical and feasible experimental animal model for PA infection drug treatment research.
王前梅;姚璞;王瑜;孙凤军
陆军军医大学第一附属医院药学部,重庆 400038陆军军医大学第一附属医院药学部,重庆 400038陆军军医大学第一附属医院药学部,重庆 400038陆军军医大学第一附属医院药学部,重庆 400038
生物科学
铜绿假单胞菌海藻酸盐珠慢性肺部感染气管插管动物模型
Pseudomonas aeruginosaalginate beadschronic pulmonary infectiontracheal intubationanimal model
《中国实验动物学报》 2026 (4)
496-504,9
国家自然科学基金青年项目(82102448).Funded by Young Scientists Fund of the National Natural Science Foundation of China(82102448).
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