| The Prophylactic and Therapeutic reseaches of chronic hepatitis B are the important issue in the field of liver diseases. Anti-virus therapy is the focus and main solution of chronic hepatitis B today. To eliminate HB V completely is the best therapeutic strategy to release hepatitis and to reduce the occurrence of cirrhosis and hepatoma. 3TC, a nucleoside analogue, which is believed to be one of the strongest anti-HBV drugs, can eliminate HBV DNA by inhibiting DNA polymerase. Unfortunately, when the administration of 12-18 months is terminated, HBV DNA recurs in the serum. This phenomenon is called withdrawal recurrence. The current therapy projects of chronic hepatitis B are not ideal to put an end to complications. Some researchers thought thatanti-hepatic-fibrosis might be an alternative strategy, the objective of which isto reduce hepatic fibrosis or delay the genesis of cirrhosis.Hepatic fibrosis is the middle link in the chain of cirrhosis genesis. Evidences of different levels had led to common insights about main mechanism of hepatic fibrosis. Every changes during the fibrogenesis, especially the activation, phenotype- differentiation, and proliferation of Hepatic stellate cell (HSC), were modulated by different cytokines, whose particular cyto-effects result from their own particular signaling pathways. This complex pathological course is modulated by cytokine network.This thesis was designed to investigate the role of DHBV replication in extrahepatic tissues in the period of withdrawal recurrence and other problemsin the anti-HBV therapy. Another aspect of the thesis is the construction of the cellular platform for screening anti-hepatic-fibrosis Traditional Chinese Medicine in vitro, and we also discuss whether or not there is any connection between the TGF-P signaling and drugs' anti-proliferation effect. These works may be helpful approaches for future reseachesin hepatitis.The study was divided into four aspects in part I of the paper: First,infected hepatitis B virus ducklings were used as the hepatitis model and their dynamic DHBV viraemia were examined. Second, PCR and dot-blot hybridization were used to examine DHBV in both liver and extrahepatic tissue and the sensitivity of two methods to detect DHBV in tissues were compared. Third, dynamic viral load in serum after treated by ACV and 3TC was observed. And the last, the pathology of liver and extrahepatic tissues were studied.The optimal concentration of MgCl2 and condition of PCR to detect DHBV were obtained after a series of experiments. PCR was more sensitive than Dot-Blot(P<0.01) so that the former is the better choice for detecting DHBV in liver and extrahepatic tissues. There was no difference in DHBV DNA detected by PCR between virus control group and drug groups (P>0.05), that is to say, nucleoside analogues could not clear DHBV-DNA in liver and extrahepatic tissues. Pathological study included in virus control group such features as hepatocyte denaturalization, swollen, vacuole or karyopyknosis, and inflammation in portal area. In AVC group and 3TC group the inflammation were alleviated but hepatocyte also has pathological features, karyopyknosis and vacuole. The reason of these phenomenon should be studied further. In these three groups, kidney and spleen had incoordinately pathological changes . But heart and lung had nonspecific pathological changes.The results of PCR and Dot-Blot hybridization for the serum sample were identical, but for the tissular samples PCR was much more sensitive than Dot-Blot. Dot-Blot appeared many fake negative results and is unsuitable to be used in this condition. Virus replication exist in extrahepatic tissues. Maybe the virus in extrahepatic tissues is not active and the immune cells could not recognize them. In respect to pharmacokintics, we speculate that drug concentration in these tissues is too low to clear up the virus. The tissueperhaps appear shelters to virus mutants. Nucleoside analogues could not eliminate the DHBV in both hepatic and extrahepatic tiss...
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