牛樟芝與橄欖多酚對小鼠酒精性脂肪肝及肝臟粒線體功能之影響

Effects of niuchangchih and hydroxytyrosol on alcoholic fatty liver and hepatic mitochondrial function in mice

葉品辰(Pin-Chen Yeh)

指導教授 ： 謝榮鴻

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2013年)

摘要

慢性過度酒精攝取會使過多的脂質累積在肝細胞，造成酒精性脂肪肝，可能會進一步惡化成肝炎、肝纖維化及肝硬化，甚至進展成肝癌。慢性酒精攝取亦會產生過多的reactive oxygen species (ROS)及自由基，形成氧化壓力，造成粒線體的功能異常、能量耗竭及細胞壞死。牛樟芝及橄欖多酚hydroxytyrosol具有良好的抗氧化力及調節生理功能。本研究以酒精性脂肪肝動物模式探討牛樟芝與橄欖多酚混合配方，改善酒精性脂肪肝及維持粒線體功能的效果。實驗動物採用7週齡雄性C57BL/6小鼠，以Lieber-DeCarli流質酒精飼料餵食，適應期2週後，隨機分為5組，分別為控制組、酒精組、低劑量組、中劑量組及高劑量組，經餵食6週後，結果顯示牛樟芝與橄欖多酚的介入可降低因酒精造成的粒線體損傷，包括增加粒線體呼吸鏈酵素的活性，增加粒線體氧消耗量，改善粒線體功能；此外，降低肝功能指標aspartate aminotransferase (AST)及alanine aminotransferase (ALT)，減少肝臟triglyceride (TG)及total cholesterol (TC)脂質含量，增加抗氧化指標glutathione (GSH)及superoxide dismutase (SOD)含量及glutathione peroxidase (Gpx)、glutathione reductase (Grd)及catalase (CAT)的活性，降低malondialdehyde (MDA)含量(p< 0.05)，在組織病理切片顯示肝細胞的受損及脂肪堆積皆有顯著的降低及改善。綜合以上結果顯示，牛樟芝與橄欖多酚添加餵食可以有效預防及改善酒精性脂肪肝疾病。

關鍵字

酒精性脂肪肝、粒線體、牛樟芝、橄欖多酚

並列摘要

Chronic alcohol consumption leads to accumulation of lipids in the liver. Consequently, there is a potential of progression to alcoholic fatty liver disease (AFLD), hepatitis, fibrosis and cirrhosis which may eventually lead to liver cancer. Reactive oxygen species (ROS) and free radicals produce by chronic alcohol consumption, contributes to oxidative stress in the liver. Oxidative stress results in mitochondrial dysfunction, energy depletion and cell necrosis. Niuchangchih (Antrodia camphorata) and hydroxytyrosol have good antioxidant capacity and physiological functions modulating ability. This study investigated the effects of niuchangchih and hydroxytyrosol on alcoholic fatty liver in mice and liver mitochondrial function. Male C57BL/6 mice (7 weeks old) were fed on Lieber-DeCarli alcohol liquid diet. After 2 weeks of adaptation period, mice were randomly assigned to five groups including control; alcohol; low dose; medium dose and high dose according to various dosages of supplements. After 6 weeks of experimental period, the niuchangchih and hydroxytyrosol interventions increased mitochondrial respiratory chain enzyme activity, increased mitochondrial oxygen consumption, and improved mitochondria functions. In addition, cotreatment of niuchangchih and hydroxytyrosol reduced serum AST, ALT, TC and TG levels, liver TG and TC levels, and increase antioxidant index of GSH, SOD, Gpx, Grd and CAT activities, decreased MDA content (p＜0.05). Histopathology analysis showed reduced damage of liver cells and lipid droplets in the treatment group compared to the alcohol group. In conclusion, these results indicate the potential of niuchangchih and hydroxytyrosol prevent and improve liver and mitochondrial function indices in alcohol liver disease.

並列關鍵字

Alcohol liver disease ； Hydroxytyrosol ； Mitochondria ； Niuchangchih

參考文獻

Ao ZH, Xu ZH, Lu ZM, Xu HY, Zhang XM, Dou WF (2009) Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases. J Ethnopharmacology 121:194-212.

Arai M, Leo MA, Nakano M, Gordon ER, Lieber CS (1984) Biochemical and morphological alterations of baboon hepatic mitochondria after chronic ethanol consumption. Hepatology 4:165-174.

Baraona E, Lieber CS (1979) Effects of ethanol on lipid metabolism. J Lipid Res 20:289-315.

Beier JI, McClain CJ (2010) Mechanisms and cell signaling in alcoholic liver disease. J Biol Chem 391:1249-1264.

Bendini A, Cerretani L, Carrasco-Pancorbo A, Gomez-Caravaca AM, Segura-Carretero A, Fernandez-Gutierrez A, Lercker G (2007) Phenolic molecules in virgin olive oils: a survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade. Molecules 12:1679-1719.