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  • 學位論文

牛樟芝對大白鼠酒精性肝發炎之保護效益及相關訊息傳導途徑探討

The Beneficial Effect of Antrodia Camphorata on Ethanol-Induced Liver Inflammation and Signaling

指導教授 : 曾博修

摘要


長期過量飲酒會引起酒精性肝病,初期表現為脂肪肝,進而發展成為酒精性肝炎、肝纖維化、肝硬化,最後還可能導致肝癌。牛樟芝是台灣特有的品種,是一種多孔性的真菌,只能寄生在台灣珍貴的林木牛樟樹上。牛樟芝具抗氧化、抗凋亡及抗發炎的作用。由過去文獻得知,牛樟芝除了能抑制癌細胞的生長,還能防止過敏,促進肝功能以及降血脂,降血壓。本篇論文將探討牛樟芝對酒精性肝炎之效益。我們利用大白鼠為動物實驗模式,在其飲水中添加20%酒精,將大白鼠肝臟誘導為酒精性肝發炎,利用不同濃度牛樟芝管餵老鼠,觀察其改善效益及減緩肝臟發炎之訊息傳遞路徑。由Gelatin zymography結果發現在餵食牛樟芝的組別中MMP9/MMP2的活性與酒精誘導肝臟發炎的老鼠組別比較有顯著的下降。而在西方墨點法(Western blot)分析中顯示,老鼠在酒精誘導肝臟發炎中,TLR-4,5,7,9蛋白表現量上升,及其下游蛋白MyD88、MAPK pathway(p-Erk、p-p38)、PI3K、AKT之表現量隨之上升及其產生之發炎因子(TNF-α、IL-1β、IL-6)表現量增加,顯示老鼠因酒精的刺激之下,造成肝臟受損。而老鼠餵食牛樟芝後,TLR-4,5,7,9有明顯下降的趨勢,伴隨著其下游蛋白MyD88、MAPK pathway(p-Erk、p-p38)、PI3K、AKT之表現量隨之下降及其產生之發炎因子表現量降低。由上述實驗結果可知,牛樟芝可減緩酒精所造成的肝臟發炎,且牛樟芝由Hsp70 dependent方式調降TLR-4,5,7,9,另外牛樟芝透過p53、p21 dependent pathway調降酒精造成之壓力,因此牛樟芝對於酒精造成的肝臟損傷確實具有抑制作用,可有效保護肝臟。

關鍵字

牛樟芝 酒精 發炎 類鐸受體

並列摘要


Alcoholic liver disease, presenting as fatty liver at the initial period, and further developing into alcoholic hepatitis, liver fibrosis, liver hardening and possibly causes liver cancer finally. Antrodia Camphorata is a rare and precious fungus in Taiwan, which has been claimed to have a variety of medical functions such as anti-cancer, anti-inflammation, anti-oxidant and liver protection. To evaluate the effects of Antrodia Camphorata on liver injury. The Wistar rats are animal experiment model. An ethanol-liver inflammation was induced by drinking water containing 20% (w/w) alcohol. Therapeutic groups were orally administrated difference dosages Antrodia camphorate on alcohol-fed rats. Observe the beneficial effect of Antrodia Camphorata on ethanol-induced liver inflammation and signaling. Significantly reduced ratio of hepatic MMP-9/MMP-2 was detected in rats of Antrodia Camphorata (AC) group compared to those of Alcohol group. In Western blotting, TLR-4, 5, 7,9, and downstream protein MyD88, MAPK pathway (p-Erk, p-p38) , PI3K, AKT, and inflammation factor (TNF-a, IL-1b, IL-6) are increases on Alcohol group. Reveal the rats stimulus of alcohol causes ethanol-liver inflammation. And after the rats feeds the Antrodia Camphorata, TLR-4,5,7,9, and downstream protein MyD88,MAPK pathway(p-Erk,p-p38),PI3K, AKT,and inflammation factor (TNF-a, IL-1b, IL-6) are decreases on AC group. Moreover, HSP70 dependent reduction of TLR-4,5,7,9 was observed in livers of rates from AC group compared to those of Alcohol group. These findings suggested the protective effects of Antrodia Camphorata on ethanol-mediated liver injury and the potential as a health supplement.

並列關鍵字

Antrodia Camphorata Ethanol liver inflammation TLRs

參考文獻


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