Toxic Heat Level Injection On The Fm <sub> 1 </ Sub> Infection In Mice

OBJECTIVEThe pharmacodynamics studies are to confirm the effectiveness of Dureping injection (DRP) on influenza viral FM₁ infected mice. Pathomorphology studies,immune regulation studies and cytokine studies are to explore the protective mechanisms of DRP of reducing immunologic injury on influenza viral FM₁ infected mice.METHODSThe experiment includes three sections:The antivirus effect of DRP injection to the FM₁ infected mice: Protection of DRP injection to the mice with influenza virus FM₁ infected:ICR mice were inoculated intranasally with mouse lung-adapted influenza virus strain(FM₁),then treated with DRP. Ribavirin and SHL injection were used as control drugs. The effect of DRP on the mortality rate and the life protection of FM₁ infected mice after 14 days inoculation was observed.The effect of DRP injection on the lung injury and the mechanism of FM₁ infected mice:â‘ The effect of DRP injection on the lung index and the lung pathological change to FM₁ infected mice. Made influenza model,the mice were treated with DRP,Ribavirin and SHL injection were used as control drugs,at the 7th day after inoculation,the mice were sacrificed,lungs were removed and weighed,then lung index was analysised;then lungs organ were fixed in formalin,routinely processed,and embedded in paraffin. Routine hematoxylin-and-eosin (H&E)-stained sections were examined.â‘¡The mice effected by influenza viru(sFM₁)were treated with DRP injection,the group treated with Ribavirin and SHL injection were the control groups,the mice were sacrificed at the 7rd day after inoculation,and lung tissue homogenate were prepared,IL-1, TNF-α, in mice lung tissue homogenate were measured with ELISA and NO was measured with Griess.The effect of DRP injection on the immune function and lymphocyte in the lung tissue homogenate to FM₁ infected mice: The mice effected by influenza virus(FM₁)were treated with DRP injection,the group treated with Ribavirin and SHL injection were the control groups,the mice were sacrificed at the 7rd day after inoculation,and lung tissue homogenate were prepared, IL-4, IL-10 in mice lung tissue homogenate were measured with ELISA. The level of T lymphocyte was measured by MTT colorimetry. The level of INF-γcontent of T lymphocyte induced with ConA was detected with ELISA. The phagecytosis production of macrophages of FM₁ infected mice was measured by Neutral Red colorimetry.RESULTSThe life protection rate of DRP1 and DRP2 are 29.1%. Compared with Model group, they are increased signifincantly (P<0.05respectively). The life protection rate of Ribavirin group is 100%, compared with Model group, it is increased signifincantly (P<0.001). The results of other groups were insignificant (P>0.05).â‘ The pathomorphology studies showed that Model group lung appearance changes were consolidation and hemorrhage;the pathological changes were serious interstitial pneumonia changes,showing bronchial epithelium shedding,alveolar interval thickening,many mononuclearcells infiltrating the alveolar wall and bronchiolar wall,producing consolidated regions,serous effusion in alveolar cavities,compensatory pulmonary edema. Compared with Model group,the pathological changes of Ribavirin group ,SHL group and DRP group were ameliorated significantly. Compared with Model group,Ribavirin group , SHL group and DRP group showed lower lung index(P<0.01).â‘¡Compared with Sham group, the content of NO in the lung tissue homogenate increased significantly mostly (P<0.001), the content of NO in the serum increased significantly (P<0.05); Compared with Model group, the content of NO of DRP group in the lung tissue homogenate decreased significantly(P<0.001); The content of NO of DRP group in the serum decreased significantly(P<0.05).â‘¢Compared with Sham group, lung tissue homogenate IL-1, TNF-αcontent of Model group increased significantly(P<0.001); The content of IL-1, TNF-αof Ribavirin group, SHL group and DRP group decreased significantly, compared with Model, P<0.001.â‘ Compared with Model, the DRP injection can improve the T lymphocyte multiplication ability and the level of cytokine INF-γof the FM₁ infected mice significantly, P<0.01;â‘¡The DRP injection can improve the level of phagecytosis production of macrophages of FM₁ infected mice significantly, compared with Model, P<0.001;â‘¢The content of IL-4 and IL-10 of the Model group is increased significantly compared with the Sham group, P<0.001; The DRP injection can improve the level of IL-4 and IL-10 in the lung tissue homogenate significantly, compared with Model group, DRP1 and DRP2 P<0.001, DRP3 P<0.001 on IL-4, P<0.05 on IL-10.CONCLUSIONThe DRP injection can enhance the life protective rate, reduce inflammatory pathology in the lung of FM₁ infected mice. These indicate that DRP is an effective injection for the influenza. Regulating the production of NO, IL-1, TNF-α, IL-4, IL-10 were the possible immunological mechanisms of DRP's therapeutical effect. Regulative effects on cytokines may be one of the factors that DRP decreases the pathogenesis of influenza-induced immunologic injury.