经肠道播散诱导内源性感染小鼠模型的建立及评价  

Establishment and evaluation of a mouse model of endogenous infection induced by intestinal dissemination

作　　者：叶先飞 陈丽[1] 王若南[1] 葛超荣[1] 陈瑜[1] YE Xianfei;CHEN Li;WANG Ruonan;GE Chaorong;CHEN Yu(the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003)

机构地区：[1]浙江省临床体外诊断技术研究重点实验室浙江大学医学院附属第一医院检验科

出　　处：《中国实验动物学报》2019年第3期291-297,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家重点基础研究发展计划(973计划)项目(2013CB531400和2013CB531605)~~

摘　　要：目的建立经肠道播散诱导发生内源性感染的小鼠模型,为研究肠道微生态与内源性感染的相关机制提供可靠的实验模型。方法24只ICR雌性小鼠随机分为模型组A、模型组B和对照组C。模型组A给予广谱抗生素溶液口服破坏肠道正常菌群后尾静脉注射5-氟尿嘧啶(5-FU)进行免疫抑制。在模型组A的基础上给予白假丝酵母菌灌胃引入机会性致病菌即为模型组B。对照组C同等方法给予生理盐水处理。实验过程中持续观察小鼠粪便菌群变化,平板计数法检测小鼠组织载菌量,HE染色观察小鼠肺、肝、盲肠和大肠组织病理变化,荧光定量PCR法观察小鼠肠道主要菌群定量变化。结果实验终点时模型组A小鼠组织器官均出现细菌感染,模型组B小鼠表现为细菌和真菌混合感染。两模型组小鼠肺和肝脏组织器官均表现为典型的炎症表现,而盲肠和大肠表现为黏膜炎症和屏障完整性被破坏。肠道菌群定量结果显示两模型组肠道主要菌群结构发生紊乱,肠道定植抗力下降,B/E值<1。结论在小鼠肠道菌群紊乱和免疫抑制的条件下,肠道致病菌或机会致病菌突破肠道黏膜屏障引起组织器官感染,该模型能够为从肠道微生态方面预防及控制内源性感染的研究提供可靠的模型基础。Objective To establish a mouse model of endogenous infection induced by intestinal dissemination and provide a reliable experimental model for studies of the mechanism of intestinal microecology and endogenous infection.Methods Twenty-four female ICR mice were randomly divided into model group A,model group B,and control group C.The mice in group A were administered a broad spectrum antibiotic solution orally to disturb the balance of normal intestinal flora,and then 5-fluorouracil was injected into the tail vein for immunosuppression.The mice in group B were administered with Candida albicans by gavage after the same treatment as the group A.The control group C was administered with normal saline by the same method.Changes of fecal flora in the mice were continuously observed during the experiment.The amount of bacteria in mouse tissues was detected by the plate counting method.Pathological changes of the lung,liver,cecum,and large intestine were observed using HE staining.Quantitative changes of intestinal flora in the mice were observed by quantitative PCR.Results At the end of the experiment,bacterial infection occurred in the tissues and organs of the mice in group A,and mixed bacterial and fungal infections occurred in the group B.Lung and liver histology of the mice in both infection groups showed typical inflammatory manifestations,while the cecum and large intestine showed mucosal inflammation and disrupted barrier integrity.Quantitation of intestinal flora showed disruption of the main intestinal flora structure in the two model groups,and the ratio of the intestinal colonization resistance index was less than 1.Conclusions Under the conditions of intestinal flora disturbance and immune suppression,intestinal pathogenic bacteria or opportunistic pathogenic bacteria break through the intestinal mucosa barrier and cause tissue and organ infection in mice.This model can provide a reliable basis for the studies on prevention and control of endogenous infection from the perspective of intestinal microecology

关 键 词：内源性感染 动物模型 抗生素 肠道菌群 

分 类 号：Q95-33[生物学—动物学]