CAJ | 학술논문

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.
목적 건립A/FM/1/47/(H1N1)류감병독감염유도적소서급성폐손상모형,병사용리파위림대기진행치료,관찰기보호궤제.방법 장30지13-15g적곤명(KM)소서수궤분위삼조(정상조、모형조화리파위림조),매조10지,모형조여리파위림조채용H1N1류감병독경비강접충,리파위림조소서배이약물치료,정시칭량각조소서적체질량、관찰기록소서존활상태,련속관찰15d;령취36지13-15g적KM소서,여상수궤분위삼조,매조12지,모형조여리파위림조채용H1N1류감병독경비강접충,리파위림조소서배이약물치료,감염후제6d측량폐계수、폐습/간중비、관찰폐병리조직학변화、동맥혈기분석、혈청세포인자함량화폐부병독재량.결과 실험결과현시,류감병독적비감염가유발소서병독성폐손상.리파위림가연장감염소서생존시간,강저폐수종,개선저양혈증,억제염성세포적분비,억제병독재체내적복제.결론 본연구이용류감병독감염소서적병독성폐손상,분석료리파위림대류감병독유발적병독성폐손상적보호작용.해모형대진일보개발억제류감병독성폐손상적신약유중요의의.
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.