臺灣博碩士論文加值系統

丙型肝炎病毒 (Hepatitis C virus; HCV)屬於黃熱病毒科 (Flaviviridae)，為含有套模的RNA病毒，帶有約9.4kb、單股、正向的RNA。丙型肝炎病毒為一人類重要的致病病源，且會造成慢性肝炎、肝硬化甚至肝癌(Hepatocellular carcinoma; HCC)的產生，然而，對丙型肝炎病毒是如何造成肝癌的產生並不清楚。
在轉殖鼠的實驗當中，丙型肝炎病毒的核心基因產物已被證明能造成轉殖鼠肝癌的產生，但是，値得思考的是在其他的研究當中，利用不同株的丙型肝炎病毒核心蛋白卻不能再現相同的結果，另外我們得知丙型肝炎病毒核心蛋白的基因序列中，尚有另一蛋白質產物－ARFP/F蛋白，而ARFP/F蛋白的表現量在各株丙型肝炎病毒也各不相同。
為了了解丙型肝炎病毒的核心蛋白與ARFP/F蛋白的致癌性，我們建構了在白蛋白啟動子(albumin promoter)的調節下表達丙型肝炎病毒的核心蛋白及ARFP/F蛋白的質體，期望能觀察到底是何者引起肝癌的產生，當然，要證實這點我們還必須製備ARFP/F蛋白的單株抗體，以便在組織切片當中，比較肝癌組織與非肝癌組織ARFP/F蛋白的表達。目前我們已經得到四株丙型肝炎病毒核基因的轉殖鼠，以及三株丙型肝炎病毒ARFP/F基因的轉殖鼠，也正準備利用這些轉殖鼠進行與致癌性相關的研究。

Hepatitis C virus (HCV) is a member of the Flaviviridae family. It is an enveloped virus with a positive-stranded RNA genome whose size is about 9.4 kb. Infection with HCV can cause severe liver diseases, e.g. chronic hepatitis, liver cirrhosis and even hepatocellular carcinoma (HCC). How HCV induces HCC is largely unknown. HCV core gene is the only HCV gene proven to be able to induce HCC in transgenic mice. However, some other laboratories cannot reproduce the same results using HCV structural genes of different HCV strains. In addition to core protein, ARFP/F (alternative reading frame protein/frameshift) protein could also be produced within HCV core gene. HCV ARFP/F protein is expressed in different levels in different HCV isolates. To study the oncogenic properties of core and ARFP/F proteins using transgenic mice, we have generated expressing plasmids of these two genes under the control of Albumin promoter. Monoclonal antibodies against ARFP/F proteins are very important for us to prove whether ARFP/F protein is involved in the development of HCC by comparing the expression of ARFP/F protein in HCC with adjacent non-HCC tissues from the same HCV patients..
At present, we have got 4 lines of transgenic mice with core gene and 3 lines of transgenic mice with F gene. The oncogenic properties of these two proteins in these transgenic mice are under investigation.

題目………………………………………………………………………………………………………2
中文摘要…………………………………………………………………………………………………3
英文摘要…………………………………………………………………………………………………4
序論………………………………………………………………………………………………………5
實驗材料與方法...……………………………………………………………………………………….9
實驗結果………………………………………………………………………………………………..14
討論……………………………………………………………………………………………………..17
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圖四……………………………………………………………………………………………………..24
附錄一…………………………………………………………………………………………………..25
附錄二…………………………………………………………………………………………………..26
參考資料………………………………………………………………………………………………..28

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