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B型肝炎及相關肝病動物模式-土撥鼠之飼養管理及實驗技術

The Woodchuck Model for the Study of HBV-associated Hepatopathy-husbandry, Management and Laboratory Techniques

摘要


土撥鼠肝炎病毒(woodchuck hepatitis virus, WHV)在型態上或基因體上皆與人類B 型肝炎病毒(human hepatitis B virus, HBV)非常類似,土撥鼠(Marmota monax)被感染後和人類感染B型肝炎病毒一樣,會造成土撥鼠之急性肝炎甚至終身帶原及產生肝癌。因此肝炎研究中心自1998年引進北美洲土撥鼠至台灣,做為人類B型肝炎病毒研究的動物模式。本文報告包括飼養管理、保定、麻醉、採血、採骨髓、以實驗方式感染接種WHV成為帶原土撥鼠、DNA疫苗、土撥鼠胎兒蛋白基因之選殖、常發疾病、肝腫瘤…等。我們將利用土撥鼠做為臨床的動物模式,來針對慢性病毒肝炎和肝細胞癌研發新的治療模式,也正嘗試利用此動物建立慢性病毒性肝炎急性發作的模式,以便進一步研究其相關肝病的發生機制以及可能的治療方法。

並列摘要


The Eastern woodchuck (Marmota monax) can be infected by woodchuck hepatitis virus (WHV). The morphology and genetic organization of WHV and diseases associated with this infection are extremely similar to human hepatitis B virus (HBV). A woodchuck infected with WHV is, thus, an ideal animal model for HBV research. This animal model was first established in Taiwan in 1998 and represents the first experience raising woodchucks in Taiwan. This report describes experiences and characteristics maintaining and using this model, including woodchuck husbandry, handling/restraints, chemical restraint/anesthesia, common diseases, hibernation, blood and bone marrow sampling, experimental WHV infection, DNA vaccination, gene therapy, cloning of the woodchuck alpha-fetoprotein gene, and pathological examination of hepatocellular carcinoma (HCC), etc. Currently, we are using WHV chronically infected woodchucks as a preclinical model to explore new therapeutic methods for chronic hepatitis Band HCC. We are also attempting to establish acute exacerbation (AE) of chronic hepatitis B in this model to dissect the underlying mechanisms of AE and develop therapeutic strategies for AE.

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