標題: 利用C型肝炎病毒次基因系統研究花生四烯酸及銻化物的抗病毒作用
Using HCV Subgenomic Replicon System to study the anti-HCV activity of the Arachidonate and Antimonial Compounds
作者: 呂光洲
Guang-Zhou Leu
林苕吟
徐祖安
Tiao-Yin Lin
John T-A. Hsu
生物科技學系
關鍵字: C型肝炎病毒;HCV;PUFAs;Anti-viral Agent
公開日期: 2004
摘要: C型肝炎病毒是引起肝硬化與肝癌的主要元兇之ㄧ,根據世界衛生組織在一九九七年統計的結果估算,全世界約有百分之三的人是C肝病毒帶原者,也就是將近有一億七千萬人是染有慢性C型肝炎病毒,就我國的衛生署疾病管制局的統計結果顯示,目前為止,約有七十萬國人染有C型肝炎,大約佔全台總人口的3.5﹪,遠高於歐、美等先進國家,再加上C型肝炎病毒並無疫苗可以防治,也沒有特效藥可以治療,目前針對慢性C型肝炎的治療都是合併使用干擾素(IFN-α)及雷巴威林(ribavirin),此一療程的最大問題在於有些人會有嚴重的副作用,諸如發燒、發炎等症狀,此外,低的治癒率亦是此一治療方式需要克服的地方,因此,為有效治療慢性C型肝炎,研發高效率及低副作用的藥物是當務之急。 C型肝炎病毒自一九八九年被鑑定出來後,其相關的研究在世界各地展開,包括有病毒學、致病機制、治療藥物的開發等,其中最大的突破之ㄧ應該是在西元二千年左右的C型肝炎病毒次基因體複製模式的發現,使人類可以更加了解此一病毒在宿主細胞內的情形,也使得針對病毒複製所開發的相關抑制藥物得以進展快速,本報告就是應用此一系統,從國衛院的藥物庫中篩選出的有效抗病毒藥物做進一步的研究,醣酸銻鈉(Sodium Stiboglucognate;SSG)為抗寄生蟲用藥,SSG具有降低C型肝炎病毒基因的能力,且與干擾素合併使用有協同性加成的抑制效果,不過此一藥物抑制病毒的機制尚待做進一步的研究,本報告中的另一具有抑制C型肝炎病毒基因的物質是多元不飽和脂肪酸,多元不飽和脂肪酸普遍存在於動植物中,常用於食品添加的營養補充劑,研究的結果顯示,多元不飽和脂肪酸可以抑制含C型肝炎病毒次基因體細胞中的C型肝炎病毒基因,而且和干擾素一起使用抑制效果更好,經由進一步的結果顯示,以花生四烯酸(Arachidonic Acid;AA)為例,隨著花生四烯酸的處理濃度提高,抑制含C型肝炎病毒次基因體細胞中的C型肝炎病毒基因效果越明顯,同時細胞內的脂肪性過氧化物的產物也隨之提高,此過氧化產物也會抑制體細胞中的C型肝炎病毒基因,此外,經由試管外的酵素活性測試結果顯示,花生四烯酸可抑制C型肝炎病毒的蛋白脢的活性,本論文的研究成果顯示,由臨床用藥及天然食品中找出具有病毒抑制效果的物質,將有助於藥物的發展,希望藉由這樣的成果,讓我們在C型肝炎防治上能有新天地。
Hepatitis C virus causes severe liver diseases, such as liver cirrhosis and hepatocellular carcinoma (HCC). Acute infections in individuals often lead to development of chronic hepatitis. In 1997, it was estimated by WHO that more than 170 million, approximate 3% of worldwide population suffer from chronic HCV infection. Pegylated interferon-α plus ribavirin is the only treatment option to combat HCV, but low curring rates and severe side effects are problems. There is no effective vaccine in the world to prevent HCV infection. Thus, more effective therapy is in urgent need due to the sever side effect and unsatisfactory curing rate of the current therapy. In this disertation, we found that polyunsaturated fatty acids (PUFAs) and sodium stibogluconate were able to exert anti-HCV activity by using HCV subgenomic replicon system. When replicon cells were treated with either compound in combination with interferon-α, synergistic anti-HCV activity was observed. The anti-HCV mechanism of sodium stibogluconate is still not clear. Whereas, the PUFAs were found to increase cellular lipid oxidative products exerting anti-HCV activity. PUFAs also abolish NS3/4A activity in vitro. Results in this study might be helpful for discovery of effective medicine to combat HCV infection.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT008728806
http://hdl.handle.net/11536/49335
Appears in Collections:Thesis


Files in This Item:

  1. 880601.pdf