流感病毒致小鼠急性肺损伤模型建立及利巴韦林干预作用研究  

Acute lung injury model induced by influenza virus in mice and the intervention effect of ribavirin

作　　者：胡秋萍[1] 戴卫平[1] 刘建兴[1] 张奉学[1] 李耿[1] 李震华[1] 陈绪林[2] 赖小平[3,4] 

机构地区：[1]广州中医药大学,广州510006 [2] 中国科学院武汉病毒所 [3]东莞广州中医药大学 [4]中医药数理工程研究院

出　　处：《国际病毒学杂志》2014年第6期244-249,共6页International Journal of Virology

基　　金：广东省高等学校珠江学者岗位计划资助项目（2011年度）;广东省自然科学基金（S2012030006598）;广东省科技计划项目（2011A030100017）;广东省自然科学基金（S2012010011143）

摘　　要：目的 建立A/FM/1/47/（H1N1）流感病毒感染诱导的小鼠急性肺损伤模型,并使用利巴韦林对其进行治疗,观察其保护机制.方法 将30只13-15g的昆明（KM）小鼠随机分为三组（正常组、模型组和利巴韦林组）,每组10只,模型组与利巴韦林组采用H1N1流感病毒经鼻腔接种,利巴韦林组小鼠配以药物治疗,定时称量各组小鼠的体质量、观察记录小鼠存活状态,连续观察15d;另取36只13-15g的KM小鼠,如上随机分为三组,每组12只,模型组与利巴韦林组采用H1N1流感病毒经鼻腔接种,利巴韦林组小鼠配以药物治疗,感染后第6d测量肺系数、肺湿/干重比、观察肺病理组织学变化、动脉血气分析、血清细胞因子含量和肺部病毒载量.结果 实验结果显示,流感病毒滴鼻感染可诱发小鼠病毒性肺损伤.利巴韦林可延长感染小鼠生存时间,降低肺水肿,改善低氧血症,抑制炎性细胞的分泌,抑制病毒在体内的复制.结论 本研究利用流感病毒感染小鼠的病毒性肺损伤,分析了利巴韦林对流感病毒诱发的病毒性肺损伤的保护作用.该模型对进一步开发抑制流感病毒性肺损伤的新药有重要意义.Objective A mouse model of acute lung injury induced by infection of influenza virus A/FM/1/47/（H1N1） was established.The mechanism of ribarivin to protect mice from lethal influenza viral infection in the mouse model by reducing the lung injury was studied.Methods Briefly,30 KM graded mice,weighted from 13 to 15 grams were randomly divided into control group,model group and ribavirin group with 10 mice in each group.Both experimental and ribavirin groups inoculated intranasally with A/FM/1/47/（H1N1） influenza virus of lethal dosage,and ribavirin was also added in ribavirin group.With 15 days of continuous administration,the survival rate and body weight loss were monitored.In parallel,36 mice were divided into 3 groups and treated the same way as previously described.6 days after virus challenge,lung histopathology,lung coefficient,lung wet weight/dry weight,arterial blood gas and viral copies were analyzed to determine the acute lung injury.Results The results showed that a mouse model of acute lung injury with virus infection characterized by diffuse alveolar damage,severe hypoxia and viral copy numbers in the bronchoalveolar lavage fluid （BALF） was established successfully in this study,and ribavirin has multiple protective effects against influenza virus infection in mice.Conclusions The model may be used for the development of new drug that can reduce the pathogenesis of human acute lung injury （ALI） induced by influenza virus infection.

关 键 词：流感病毒 病毒性肺损伤 动物模型 利巴韦林 

分 类 号：R563[医药卫生—呼吸系统]