Effect of Zizheng Dihuang Mixture(紫正地黄合剂)on the Expression of Interferon Type Ⅰ and ISG in Mice with RSV Upper Respiratory Tract Infection
Objective:To explore the effect of Zizheng Dihuang mixture on the expression of type Ⅰ interferon and ISG in mice infected with respiratory syncy-tial virus(RSV).Methods:Totally 36 Balb/c mice were randomly divided into blank group(group A),model group(group B),Zizheng Dihuang mixture low dose group(group C),Zizheng Dihuang mixture medium dose group(group D),Zizheng Dihuang mixture high dose group(group E)and ribavirin group(group F),with 6 mice in each group.After 3 days of RSV nasal drip,groups C,D and E were treated with Zizhengdihuang mixture at concentration of 180.0 mg/(kg·d),360.0 mg/(kg·d),and 720.0 mg/(kg·d)respectively.Group F was treated with ribavirin at a concentration of 27.6 mg/(kg·d).The drugs was administered orally with 200 μL of physiological saline solution.Groups A and B were given the same volume of saline 200 μL once a day for 3 consecutive days.After 72 hours,the nasopharyngeal tissues of mice were taken as samples,and the levels of serum IFN-α and IFN-[3 were detected by ELISA.The pathological changes were observed by HE,and the expressions of RSV-F protein and interferon stimulating gene(ISGs)were detected by IHC.The expressions of RSV mRNA and ISG mRNA were detected by RT-PCR.Results:Compared with group A,IFN-α and IFN-β increased in other groups(P<0.01);Compared with group B,IFN-α and IFN-β increased in group C,D,E and F(P<0.01);There was no significant difference in IFN-α and IFN-β between group E and group F(P>0.05).The nasopharyngeal tissue structure of mice was normal in group A,and there were no viral particles and inflammatory changes.There were a large number of viral particles and viral inclusion bodies in group B,and the inflammation was severe.The viral particles,proliferation and inflammation of mucosal epithelium in group C,D and E were lighter than those in group B.The structure of mucosal epithelium was still damaged in group F,with a small number of epithelial hyperplasia and inflammatory cells and a small amount of virus particles.RSV-F and ISG protein antigens could be seen in the modeling groups.The epithelial cells and acini were widely infected and the cilia were exfoliated in group B.Compared with group B,a small amount of epithelial cell infection was found in group C,D and E.Group F showed less infection than group B.Compared with group A,RSV mRNA and ISG mRNA were significantly expressed in the nasopharyngeal tissues in other groups.Compared with group B,the expression of RSV mRNA decreased in group C,D,E and F(P<0.01),and the expression of ISG mRNA increased in group D,E and F(P<0.01).Compared with groups C and D,the expression of RSV mRNA decreased more significantly in group F(P<0.01),but there was no significant difference in RSV mRNA and ISG mRNA between group E and group F(P>0.05).Conclusion:Zizheng Dihuang mixture can improve the upper respiratory tract inflammation in RSV infected mice,reduce the load of RSV in nasopharyngeal tissue,and regulate the immune response by up-regulating the expression of type Ⅰ interferon and ISG in the signal pathway.It is suggested that Zizheng Dihuang mixture plays an important role in anti-RSV and controlling RSV upper respiratory tract infection.