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  • 學位論文

?雙黃酮與黃?對腸病毒抑制效果之評估

Assessment of the inhibiting effectiveness on the enterovirus by biflavonoids and Coptis chinensis

指導教授 : 吳正男 李憲明

摘要


腸病毒71型為一重要之人?致病性病毒。1998 ?間曾在台灣地區爆發大??,造成超過12萬名嬰幼童受到感染,並有 78 ?重症致死的案?。該病毒於1969?在美國加州首次被分?出?,分?上被歸?於小病毒科中之腸病毒屬,為一單向正股之 RNA 病毒。至今世界各地每?均有腸病毒之偶發感染或地區性??,其中以熱帶或亞熱帶地區較為普遍,在?床上之症?以手口足疾病為主,常會造成中樞?經之損傷而形成重症,甚至導致死亡。目前尚無腸病毒71型有效之藥物或疫苗,於是本?文之目的係從天然植物萃取物中尋找有效抑制腸病毒之藥物。試驗之結果顯示,?雙黃酮之 amentoflavone 及黃?的水粗萃取物均可有效?低腸病毒71型的感染活性,影響病毒生長曲線。病毒進?細胞吸附時同時加入藥物,可抑制病毒的病毒斑生成?目,顯示藥物可影響病毒”進入”細胞之步驟。於病毒進入細胞後才添加藥物於培養基中,可影響病毒負股 RNA 的生成速?,並影響病毒蛋白質的產?與減慢病毒所誘發的細胞病變現象。實驗結果顯示病毒的生活史可被藥物抑制在吸附、RNA 複製與蛋白質生成等關鍵步驟。而?用 ICR 小鼠所進?之動物實驗,也顯示上述成份有助於抵抗致死病毒劑?的感染,並提高受感染小鼠之存活?。此外, amentoflavone 對同為腸病毒屬之克沙奇病毒 B3、B4 和 B5 也具有抑制效用。綜合研究結果得知,amentoflavone 在未?發展為抗腸病毒71型藥物上,具有極大的潛?。

關鍵字

腸病毒71型 ?雙黃酮 黃?

並列摘要


Enterovirus 71 (EV71), an important human pathogenic virus,belonged to the Enterovirus genus of Picornaviridae family. Picornavirus is a small, non-enveloped virus with positive single-stranded RNA. In 1998, there was a large enterovirus outbreak caused by EV71 in Taiwan, causing more than 120,000 infected and 78 deaths. In each year, chance or regional outbreaks of enterovirus infection are reported all over the world, especially in the tropical and sub-tropical regions. The pre-school children are most vulnerable to EV71 infection. EV71 infection may cause some clinical symdromes, mainly hand, foot and mouse disease, and is notable for its invasion to central nervous system (CNS), leading to neurological defects and even death. Since there is no vaccine or antiviral agent available to be effective in treating or preventing EV71 infection, the specific aim of this study is to search for some extracts from natural plants that can inhibit enterovirus infection. The results showed that amentoflavone and the crude aqueous extract of Coptis chinensis are effective in inhibiting viral activity. The decrease of plaque reproduction in either drug treated virus at “absorption” stage implies viral replication was blocked at early stage of life cycle. Western blot and RT-PCR analysis indicated that amentoflavone can inhibit the translation of the virus and viral RNA synthesis. In the animal assessments, amentoflavone or the crude aqueous extract of Coptis chinensis treatments increased the survival rate of ICR mice that were challenged with lethal dose of virus. The results of in vivo and in vitro assays provided evidence that EV71 activity was efficiently inhibited by amentoflavone or the crude aqueous extract of Coptis chinensis, which may be considered as an antiviral drugs. In addition, amentoflavone was found to have inhibitory effects on other enteroviruses, including coxsackievirus B3, coxsackievirus B4 and coxsackievirus B5.

並列關鍵字

Coptis chinensis enterovirus 71 biflavonoids

參考文獻


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