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  • 學位論文

龍葵萃取物抑制以AAF誘導大鼠肝纖維化及肝癌

Solanum nigrum L. extract inhibits AAF-induced liver fibrosis and liver cancer in rats

指導教授 : 王朝鐘
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摘要


癌症預防工作已成為世界性趨勢,因此尋找可靠且有效之化學預防物質實為目前重要工作。本實驗室先前發現龍葵(Solanum nigrum)具有抑制癌細胞生長之能力,另外也利用九種不同的人類腫瘤細胞,分析其中對於龍葵較具有感受性的細胞株,結果發現,在肝癌細胞中具有高度的感受性(HepG2 與Hep3B),顯示龍葵萃取物確實具有抑制肝癌之潛力,因此本研究擬深入探討龍葵萃取物(SNWE) 對於抑制化學性致癌物質(2-acetylaminofluorene, AAF) 誘導實驗動物肝癌產生之作用及其中相關之分子機制。首先我們以AAF 在五個月處理下,誘導大鼠產生肝纖維化之模式,評估SNWE 之作用,因肝纖維化是肝癌發展早期的一項重要指標,藉由在SNWE 處理之下,觀察大鼠肝纖維化減緩之程度。由肝臟外觀可以發現,SNWE 有效地減緩肝臟纖維化的趨勢,而由肝臟的重量變化也可以發現,SNWE 具有阻止肝臟異常腫大的情形,其中SNWE 也能夠有效降低血中肝發炎指標GOT、GPT 及γ-GT的上升,而在AAF 誘導下,實驗動物的死亡率,也因為有SNWE 的加入,而有明顯地回升。我們也同時進行AAF + NaNO2在長時間誘導之模式下,誘導動物自發性產生肝癌之試驗當中,可以進一步評估SNWE 抑制肝癌發生之效用,並利用免疫染色(IHC),確定所誘發出來的肝癌,結果發現SNWE處理的組別的確可抑制肝癌的發生,並配合分析肝臟中相關之解毒酵素GST、HO-1 的表現與活性變化,及進一步分析其中之相關分子機轉,以了解SNWE 的作用機制。

關鍵字

龍葵 肝纖維化 肝癌

並列摘要


Liver cancer is one of the most frequent human cancers worldwide. Therefore the liver cancer research gradually is also important in chemoprevention. Solanum nigrum L. water extract (SNWE) had report many item of anti- cancers. In this study, we found that dietary administration of SNWE (1%, 2%) had makerly suppressed AAF-induced liver cirrhosis and liver cancer in wistar rats. On the other hand, we observed the serum levels of some important enzymes in liver such as ALT, AST, α-FP and γ-GT which were decreased by SNWE treatment after AAF-induced. Further we analysed the change by western blotting, immunohistochemistry, EMSA and some enzyme activities like GSTα, GSTμ, GSTπ and HO-1. Remarkably, SNWE increase detoxifying enzyme in AAF-induced liver and reduce liver of the damage. In summary, our data support that SNWE had exhibited antitumor potential of HCC in rats.

參考文獻


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