| 摘要: | 飽和脂肪對於酒精性肝臟疾病 (alcoholic liver disease)之影響並無定論，推測可能與飽和脂肪的來源以及油脂脂肪酸組成有關，因此，本研究利用大白鼠動物模式探討動物性與植物性飽和脂肪對於酒精性肝臟疾病之影響。本研究使用八週齡雄性Wistar大白鼠60隻，經過一週預養後，依照血漿ALT (alanine aminotransferase)、AST (aspartate aminotransferase)活性分成六組，分別為控制組 (C)、豬油控制組 (CL)、可可脂控制組 (CC)、酒精組 (E)、豬油酒精組 (EL)、可可脂酒精組 (EC)。C組以不含酒精之液體飼料餵養，E組以酒精液體飼料餵養，而CL、EL組及CC、EC組分別以90%之豬油或可可脂以及10%之大豆油作為油脂來源。各組以等熱量方式進行餵養。本研究於實驗進行八週之後進行實驗動物犧牲，並採集血液及肝臟樣品進行分析。實驗結果發現，血漿AST及ALT活性於實驗期第八週時，攝取酒精的組別皆顯著高於C組。肝臟病理切片評分結果方面，E組在脂質堆積、炎症細胞浸潤以及肝細胞變性與壞死的評分皆顯著高於C組，而EL組及EC組在炎症細胞浸潤及肝細胞變性與壞死的評分皆顯著低於E組。脂質代謝測定在肝臟三酸甘油酯 (triglyceride, TG)濃度部分，E組顯著高於C組，而E組與EL組及EC組相比皆無顯著差異，而血漿總膽固醇 (total cholesterol, TC)及高密度脂蛋白膽固醇 (high-density lipoprotein cholesterol, HDL-C)濃度部分，E組與C組相比無顯著差異，而EL組及EC組皆顯著高於E組。另外，血漿低密度脂蛋白膽固醇 (low-density lipoprotein cholesterol, LDL-C)濃度的部分，E組顯著低於C組，而EL組及EC組皆顯著高於E組。氧化壓力指標之肝臟TBARS (thiobarbituric acid reactive substances)含量方面，E組與C組相比無顯著差異，EC組顯著高於E組，而肝臟CYP 2E1 (cytochrome P450 2E1）蛋白質表現量，E組顯著高於C組，而與E組相比，EL組有增加的趨勢，EC組則有降低的趨勢 (p >0.05)。發炎反應相關指標血漿ICAM-1 (intercellular adhesion molecule 1)濃度部分，E組顯著高於C組，而EL組及EC組皆顯著低於E組。另外，肝臟IL(interleukin)-1β濃度部分，E組顯著高於C組，而EL組及EC組顯著低於E組；在IL-6、IL-10及TNF-α (tumor necrosis factors-α)濃度部分，E組與C組相比無顯著差異，而EL組及EC組皆顯著低於E組。另外，在相關性統計結果發現，肝細胞變性與壞死之評分與大白鼠紅血球中油酸百分比 (C18:1)呈顯著正相關性，然而與亞麻油酸 (C18:2)百分比呈顯著負相關性。由以上實驗結果可知，長期餵養大白鼠酒精液體飼料的模式下，以豬油或可可脂作為液體飼料中油脂來源，可藉由降低血漿中ICAM-1濃度以及肝臟IL-1β、IL-6、IL-10及TNF-α濃度而改善酒精所造成的肝損傷。並推測飽和脂肪中亞麻油酸比例與酒精誘導產生之肝臟發炎反應具有密切之相關性。
This study was to clarify the role of saturated fat from animals and vegetables works on alcoholic liver damage under chronic ethanol feeding. Male Wistar rats were divided into six groups according to aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and fed with either control diet or ethanol diet, in which containing either saturated fat (lard and cocoa butter) or unsaturated fat (corn oil, olive oil and safflower oil). The groups were control group (C), control diet with lard group (CL), control diet with cocoa butter group (CC), ethanol group (E), ethanol diet with lard group (EL), ethanol diet with cocoa butter group (EC). Rats were sacrificed after 8 weeks. Results showed that plasma AST and ALT activities, hepatic triglyceride (TG) levels, plasma intercellular adhesion molecular-1 (ICAM-1) levels, hepatic cytochrome P450 2E1 (CYP2E1) protein expression, and hepatic interleukin (IL)-1β were significantly increased in the E group compared with the C group (p<0.05). In addition, hepatic histopathological analysis scores of fatty change, inflammatory cell infiltration and degeneration and necrosis in the E group were significantly higher compared with the C group (p < 0.05). However, plasma ICAM-1, hepatic IL-1β, IL-6, IL-10 and tumor necrosis factor (TNF)-α levels were significantly decreased in the EL and EC group than those in the E group (p < 0.05). The hepatic histopathological analysis scores of inflammatory cell infiltration and degeneration and necrosis in the EL and EC group were significantly lower than those of the E group (p < 0.05). Moreover, correlation analysis showed that hepatic histopathological analysis scores of degeneration and necrosis were significantly positively correlated with C18:1 fatty acid concentrations in red blood cells, while negatively correlated with C18:2 fatty acid concentrations in red blood cells. The results suggested that chronic ethanol feeding caused hepatic fatty changes, inflammation and increased oxidative stress in rats. However, both of lard or cocoa butter could protect the liver against the inflammatory response by means of decreasing plasma ICAM-1 and hepatic cytokine levels in rats under chronic ethanol-feeding. It is speculated that the fatty acid composition of dietary fat particularly C18:2 may play a significant role in the progression of ethanol-induced liver injury. |
