犀角地黄汤合银翘散对流感病毒性肺炎小鼠肺病毒滴度和肺组织病理改变的影响

Influences of Xijiaodihuang Decoction combined with Yinqiao Powder on virus titer and pathological changes of lung tissue in mice with influenza viral pneumonia

目的观察经典合方犀角地黄汤合银翘散对流感病毒感染致病毒性肺炎小鼠的治疗作用,分析病毒滴度与肺组织病理改变的关系。方法 ICR小鼠120只随机分为6组:正常组,模型组,犀角地黄汤合银翘散中药高、中、低剂量组,利巴韦林组,25μL 50LD50病毒液滴鼻建立流感病毒鼠肺适应株感染的小鼠肺炎模型(除正常组外),感染后1 h,正常组和模型组予以双蒸水灌胃;中药高、中、低剂量组分别给予中药46、23、11.5 g/(kg.d)灌胃;利巴韦林组腹腔注射利巴韦林注射液0.1 g/(kg.d);各组均给药2次/d,连续给药7 d。每日观察小鼠的生存率、平均存活天数,体重、体温的变化至感染后14 d。BALB/c小鼠72只随机分为4组,正常组、模型组、中药中剂量组和利巴韦林组,在感染后的24、6、d分别取材,动态观察小鼠肺匀浆中病毒血凝滴度、肺组织切片在光镜和电镜下的病理改变。结果临床等效剂量(中剂量)的犀角地黄汤合银翘散可明显降低感染小鼠的死亡率,延长生存时间,增加体重和升高体温。感染组肺病毒滴度在第2天最高,随后显著下降,而肺组织病理改变在第6天达高峰,二者不同步。犀角地黄汤合银翘散在第2天可降低肺匀浆中的病毒滴度,第4天、第6天与模型组比无差异;在第6天可明显减轻感染小鼠肺组织炎症病变。结论犀角地黄汤合银翘散对小鼠流感病毒性肺炎有明显的治疗作用,直接的抗病毒增殖非其主要作用,可能主要通过抑制机体的炎症级联反应发挥作用。

Objective To observe the therapeutic effect of classical combined formula-Xijiaodihuang Decoction combined with Yinqiao Powder on influenza viral pneumonia in mice,and analysis the relationship between viral titer and pathological changes in lung tissue.Methods ICR mice（n=120） were randomly divided into the normal group,model group,three groups with different doses of Xijiaodihuang Decoction combined with Yinqiao Powder and ribavirin group.The mouse model of viral pneumonia infected influenza virus mouse lung-adapted strain was established by inoculating intranasally 50LD50（25 μL） viral suspension in all groups except the normal group.After the infection for one hour,the normal group and control group were intragastrically given double distilled water;the high-dose,mid-dose and low-dose groups were intragastrically given Xijiaodihuang Decoction combined with Yinqiao Powder [46 g/（kg·d）,23 g/（kg·d） and 11.5 g/（kg·d） respectively].The ribavirin group was injected intraperitoneally ribavirin [0.1 g/（kg·d）].All groups were treated twice a day and for 7 days.The survival rate,average survival days,body weight and temperature changes were observed everyday until to the 14th day.BALB/c mice（n=72） were randomly divided into the normal group,model group,group with middle dose of Xijiaodihuang Decoction combined with Yinqiao Powder（mid-dose group） and ribavirin group.On the 2nd,4th and 6th day of infection,the viral HA titer in lung homogenate and pathological changes of lung tissue under the optical microscope and electron microscope were observed dynamically.Results The clinical equivalent dose（middle dose） of Xijiaodihuang Decoction combined with Yinqiao Powder decreased significantly the mortality,prolonged the survival time,increased the bodyweight and elevated temperature in mice with viral pneumonia.In the model group the viral titer in lung reached the peak on the 2nd day,and then decreased significantly,but the pathological changes of lung tissue reached the peak on the 6th day.The viral titer was decreased in lung homogenate in the mid-dose group on the 2nd day,which on the 4th and 6th day had no significant difference compared with the model group.On the 6th day Xijiaodihuang Decoction combined with Yinqiao Powder relieved significantly the inflammation of lung tissue in infected mice.Conclusion Xijiaodihuang Decoction combined with Yinqiao Powder has an apparent therapeutic effect on influenza viral pneumonia in mice.The major effect is to inhibit inflammatory cascade rather than anti-viral effect.