Effect Of Estriol On Hepatitis B Virus Transcription And Replication

Background: Hepatitis B virus(HBV)infection is the main cause of acute and chronic hepatitis,and can gradually develop into liver cirrhosis and liver cancer.HBV infection is a serious threat to human health in the world.At present,the main drugs for hepatitis B patients include interferon and nucleoside analogues.Interferon is only effective for less than 30% of patients,and its side effects are large,so its application is limited.The long-term use of nucleoside analogues(NAS)may cause the problem of virus resistance.Therefore,in order to further improve the therapeutic effect of hepatitis B patients,it is necessary to identify new antiviral factors.Estriol(EST)is one kind of estrogen existing in human body.More and more reports show that estrogen is related to the gender differences in the epidemiology of chronic HBV infection and HBV related liver cancer.It has also been reported that estriol can affect the replication level of many viruses in vitro,but whether estriol can directly affect the life cycle of HBV remains to be studied.Objective:To study the effect of estriol on the transcription and replication of hepatitis B virusMethods:1.The CC50 values of estriol in HepG2.2.15 cells and HepG2-NTCP cells was analyzed by MTS,so the cytotoxicity of estriol was detected.2.Different concentrations of estriol were added to HepG2.2.15 cells and HepG2 NTCP cells.RT-qPCR was used to detect the effect of estriol on HBV DNA and HBV RNA levels.ELISA was used to detect the effect of estriol on HBsAg and HBeAg secretion.3.The HBV transgenic mice(C57BL/6)were treated with 5mg/kg estriol intraperitoneally.The levels of AST andALT were detected by colorimetric assay.The levels of HBsAg and HBeAg were detected by ELISA.The levels of HBV DNA in serum and HBV DNA and HBV RNA in liver tissue were analyzed by RT-qPCR.Results:1.The CC50 of estriol in HepG2.2.15 cells and HepG2-NTCP cells were 181.5 ?mol/L and 218.6 ?mol/L,respectively.2.10 ?mol/L,20 ?mol/L and 40 ?mol/L estriol could reduce the level of HBsAg and HBeAg secreted by HepG2.2.15 cells and the level of HBV DNA and HBV RNA in HepG2.2.15 cells(P < 0.05).3.10 ? mol/L,20 ? mol/L and 40 ? mol/L estriol could reducethe level of HBsAg and HBeAg secreted by HepG2-NTCP cells and the level of HBV DNA and HBV RNA in HepG2-NTCP cells(P < 0.05).4.In HBV transgenic mice,estriol had no significant effect on the levels of AST and ALT in serum;estriol could significantly reduce the levels of HBsAg,HBeAg,HBV DNA in serum and HBV DNA and RNA in liver tissue(P < 0.05).Conclusion:In our study,we researched the effect of estriol on HBV replication.The data indicated estriol could inhibit the transcription and replication of HBV in HepG2.2.15,HepG2 NTCP cells and HBV transgenic mice.