Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding o...Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.展开更多
Previous study on TNFRl-mediated hepatocyte apoptosis has been implicated in the development of fulminant viral hepatitis. To interfere with the potentially effective target, plasmid named p-mTNFRlshRNA complimentary ...Previous study on TNFRl-mediated hepatocyte apoptosis has been implicated in the development of fulminant viral hepatitis. To interfere with the potentially effective target, plasmid named p-mTNFRlshRNA complimentary to the sequence responsible for mTNFR1 was also constructed and further confirmed by sequence analysis. To investigate the effect of mTNFRlshRNA plasmid on mTNFR1 expression in vivo and the disease progress in MHV-3 induced fulminant hepatitis mice model. By hydrodynamic injection of mTNFRlshRNA plasmid, the survival rate of mice, hepatic pathological change were examined and compared between mice with/without mTNFRlshRNA plasmid intervention. The expression of mTNFR1 was detected by Real-time PCR, immunohistochemistry staining. The mTNFRlshRNA plasmid significantly reduced mTNFR1 expression in vivo, markedly ameliorates inflammatory infiltration, prolonged the survival time period and elevated the survival rate from 0 up to 13.3% in Balb/cJ mice with MHV-3 induced fulminant hepatitis. This study was designed to explore the opportunity of RNA interference technique in inhibiting TNFR1 expression, which has been reported to be involved in the development of a variety of diseases including fulminant viral hepatitis and severe chronic hepatitis B.展开更多
文摘Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.
基金National Science Fund of China(NSFC)(30571643,30672380,30700702)National Key Basic Research Program of China(2005CB522901,2007CB512900)
文摘Previous study on TNFRl-mediated hepatocyte apoptosis has been implicated in the development of fulminant viral hepatitis. To interfere with the potentially effective target, plasmid named p-mTNFRlshRNA complimentary to the sequence responsible for mTNFR1 was also constructed and further confirmed by sequence analysis. To investigate the effect of mTNFRlshRNA plasmid on mTNFR1 expression in vivo and the disease progress in MHV-3 induced fulminant hepatitis mice model. By hydrodynamic injection of mTNFRlshRNA plasmid, the survival rate of mice, hepatic pathological change were examined and compared between mice with/without mTNFRlshRNA plasmid intervention. The expression of mTNFR1 was detected by Real-time PCR, immunohistochemistry staining. The mTNFRlshRNA plasmid significantly reduced mTNFR1 expression in vivo, markedly ameliorates inflammatory infiltration, prolonged the survival time period and elevated the survival rate from 0 up to 13.3% in Balb/cJ mice with MHV-3 induced fulminant hepatitis. This study was designed to explore the opportunity of RNA interference technique in inhibiting TNFR1 expression, which has been reported to be involved in the development of a variety of diseases including fulminant viral hepatitis and severe chronic hepatitis B.
