磷酸奥司他韦不同时序干预对A型H1N1流感病毒感染小鼠模型药效及炎症因子调控作用研究

Study on efficacy and regulation of inflammatory factors with oseltamivir phosphate by different time series of interventions in a murine model of influenza A H1N1 virus infection

目的针对目前抗病毒体内实验给药时间点偏早的现状,本研究以磷酸奥司他韦(达菲)作为“工具药”,比较不同时序干预对病毒感染小鼠的影响,为抗病毒药物研究选择合理的模型干预时间点提供依据。方法将Balb/c小鼠随机分成6组,滴鼻感染流感病毒(0.25 TCID_(50))建立病毒感染小鼠模型,达菲-1组、达菲-2组分别在染毒后d 1和d 4灌胃给药。测定体质量,计算生存率、脏器指数,测定病毒载量及炎症因子含量。结果与空白对照组比较,模型组小鼠的体质量降低,肺指数均明显升高(P<0.05);模型-2组13个炎症因子表达水平差异有显著性(P<0.05)。与模型-1组相比,达菲-1组肺指数、脾指数明显降低(P<0.05),病毒载量为模型-1组的0.54倍;与模型-2组相比,达菲-2组肺指数明显降低(P<0.05)、胸腺指数明显升高(P<0.05),病毒载量为模型-2组的0.03倍,13个炎症因子表达水平差异具有显著性(P<0.05)。结论方案2的小鼠染毒后症状更明显、稳定、给药后减轻了肺部炎症损伤,考虑了潜伏期,待模型动物出现症状开始进行药物干预符合临床用药指征,无论是在模型评估还是药物评价将更合理和准确。

Aim To compare the effects of different time sequence interventions on virus infected mice by using oseltamivir(Tamiflu)as a“tool drug”in view of the current situation of the too early the administration time of antiviral in vivo experiment,so as to provide a basis for selecting a reasonable model intervention time point for antiviral drug research.Methods Balb/c mice were randomly divided into six groups.The virus infection model was established by intranasal infection with influenza virus(0.25 TCID_(50)).Tamiflu-1 group and Tamiflu-2 group were administered orally on 1st and 4th day after exposure.The body mass,survival rate,organ index,viral load and inflammatory factor content were measured.Results Compared with the blank control group,the body weight of the mice in the model group decreased and the lung index increased significantly(P<0.05).The expression levels of 13 inflammatory factors in model 2 group were significantly different(P<0.05).Compared with the model-1 group,the lung index and spleen index of the Tamiflu-1 group decreased significantly(P<0.05).Compared with the mode-2 group,the lung index in the Tamiflu-2 group was significantly lower(P<0.05),and the thy-mus index was significantly higher(P<0.05).The viral load was 0.03 times that of the model-2 group. The expression levels of 13 inflammatory factors were significantly different ( P< 0.05). Conclusions The symptoms of the mice in Scheme 2 are more obvious and stable after exposure. After administration,the lung inflammation damage is alleviated. Considering the latency,drug intervention is in line with the clinical drug indications when the model animals show symptoms. It will be more reasonable and accurate whether in the model evaluation or drug evaluation.