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The Pharmacological Study Of YZK Compound In Treating Hepatitis B

Posted on:2009-11-19Degree:MasterType:Thesis
Country:ChinaCandidate:Z H GanFull Text:PDF
GTID:2144360272962115Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
The anti-viral therapy of chemistry in clinic is based on the inhibition of distinctive hepatic DNA replication,which can reduce the replication of cccDNA and can inhibit the expression of the target antigen in infected cells to alleviate inflammatory.It is important to clean hepatic cells' cccDNA on the last treatment of chronic B- hepatitis.At present,the combination treatment includes anti-viral chemistry,immune regulation,therapeutic vaccines and gene targeting therapy.Compounds of Chinese herbal in the clinical treatment of hepatitis are widely used.From Some researches,we recognizes that compounds of Chinese herbal were useful in inhibiting the replication of virus,regulating immune functions,reducing injuries of the liver cell and improving liver functions,especially in curing fibrosis and early cirrhosis of liver.The global efficacy is better than single chemical medicine.The YZK compound is based on Yinchenhao reagent,composed by Yinchen, Zhizi and Kushen in different dose.In this study,we evaluated the efficacy of YZK compound to hepatitis by using 2.2.15 cell model and B-hepatitis duck model,and discussed the mechanism of anti-hepatitis by the compound.Controlled with Lamivudine,we detected the cytotoxic of compound and the inhibition to HBsAg, HbeAg.Through establishing SyBr green I fluorescent real-time quantitative PCR method of HBV DNA and B-hepatitis duck model on observing the inhibition of DHBV DNA in body,we got the a method on evaluating drug efficacy.In this study,we observed the action YZK compound to the expression about HBeAg and HBsAg in 2.2.15 cellular centrifugal liquid and the inhibition of HBV DNA.In toxicity tests,YZK compound' TC0 was 200 mg/ml and TC50 is 358.5 mg/ml to HepG2.2.15.YZK compound and its components could inhibit the HBsAg in 2.2.15 cellular centrifugal liquid in all.Though the inhibition levels were different,but its basic trends were alike.It was that the inhibition rose from the first day,achieved the highest level at the sixth day and decline after.Among the compounds and its components,the inhibition of high dose compound was highest and was marked difference between 3TC.In trends of inhibition rate to HBsAg,the effect of high dose compound declined most slowly and lasted longest,which was alike with HBeAg. Other groups' inhibition rate to HBeAg changed between the 20 percent to 30 percent, which were not significant and instability.In trends of inhibition rate to HBeAg,the inhibition effect of high dose compound declined and lasted in short time.From results,we considered that the inhibition of compound to HBsAg was stronger than to HBeAg.From the inhibition effect to HBsAg in 2.2.15 cellular centrifugal liquid by compound serum,the peak of curve appeared at the sixth day and after that gradually declined also.Although the trend declined more slowly than the pure drug,at the twelfth day,the level still was higher.There was no significant difference in the inhibition of two compounds serum to HBsAg.From the inhibition to HBeAg in 2.2.15 cellular centrifugal liquid by compound serum,its curve was different to HBsAg.Though the peak was at the sixth day also,but after that there was no significantly declination.At the twelfth day,the inhibition rate remained highly and stably.There was no significant difference in the inhibition of two compounds serum to HBeAg.From the experimental results,we found that the high-dose YZK compound played a significant role about some indicators in out-body experiment and differenced with control group.The inhibition of YZK compound to the virus DNA increased with increasing dose and there was a dose-effect relationship.The inhibition rate of the high-dose YZK compound was similar with Lamivudine.The high-dose YZK compound and Lamivudine were less an index level than the control group in HBV copy and theirs effects were good.The inhibition of Kushen to HBV DNA was strongest in components of YZK compound,its effect was between in high dose and in low dose.The inhibition to HBV DNA of Yinchen was poor.So we concluded that Kushen played the important role to anti-HBV DNA in the compound and the inhibition of compound was stronger than three simple components(the extract of Yinchen,the extract of Zhizi and the extract of Kushen).Concurrently,the effect of compound couldn't be simply regarded at the sum of components.The effect of high dose and low dose compound was better than single component.In this study,we observed the influence of the HBV DNA replication to the anabolism serum of YZK compound through fluorescence quantitative testing method. From the results,controlled with negative serum,there was little inhibit,the rate was no more than 20 percent.In this study,we observed the inhibition of body-anabolism with compound to DHBV DNA replication by B-hepatitis duck model.Through oral and celio- injection medication,and setting up five groups(control group,3TC group,low dose group secondary dose group and high dose group),to take samples at the day before taking medicine(T0),the fifth day of taking medicine(T5),the tenth day of taking medicine (T10) and the three after day of stopping medicine,we applied ANOVA with repeated measures by inhibition rate.From the results,we recognized that there was difference in statistics between oral and celio-injection medication,there was difference in statistics between the inhibition at T5 and T10,there was no difference in statistics between the inhibition at T5 and P3,there was difference in statistics among control group and other groups,there was no difference in statistics among the three compound groups,and there was difference in statistics among 3TC group and others exclude high dose group.So we concludes that it was effective in inhibiting DHBV DNA replication by the compound and the effect of celio- injection medication was better than oral.It was similar between high dose groups with 3TC group,although high dose wasn't enough better with 3TC in curative effect.There was no difference in statistics among the three compound groups,it maybe relate with little samples. We thought the relationship of therapy efficiency and compound doses need more investigate by increasing samples.
Keywords/Search Tags:Hepatitis B (HB), Hepatitis B Virus (HBV), HepG2.2.15 Cells, B-hepatitis Duck Model, YinZhiKu Compound
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