- 學位論文
樹葡萄預防酒精性肝損傷之研究
Myrciaria Cauliflora extracts prevent alcohol-induced liver damage
摘要
慢性肝病在台灣的死亡率高居第九，而酒精是造成肝病的主因之一，可引起氧化壓力、免疫反應及發炎與脂肪的堆積，而對肝臟細胞造成傷害。俗稱樹葡萄的嘉寶果富含多樣花青素，具高抗氧化力，然而其對酒精性造成的肝損傷脂作用尚未釐清，因此本研究針對其在酒精誘導小鼠肝臟的作用進行實驗。動物實驗結果顯示，樹葡萄 (MC)能降低酒精誘導小鼠肝功能指數AST、ALT及血清中三酸甘油脂與膽固醇的含量，並促進肝臟內抗氧化酵素Superoxide dismutase (SOD)、catalase、glutathione peroxidase (GSH-Px)的活性減輕酒精所造成的氧化壓力，此外MC也能透過活化AMPK路徑，抑制脂肪生成相關因子如sterol regulatory element-binding protein (SREBPs)、fatty acid synthesis (FAS)、acetyl CoA carboxylase (ACC)等蛋白抑制三酸甘油脂與膽固醇的合成，並活化脂防氧化與運輸因子如peroxisome proliferator-activated receptor α (PPAR-α)、carnitine palmitoyl transferase 1 (CPT1)、microsomal triglyceride transfer protein (MTP)等蛋白促進脂肪酸氧化。MC也抑制了酒精引起的巨噬細胞下游發炎因子如NF-κB、TNF-α、IL-6、MCP-1、COX-2、iNOS等的活化，減輕酒精引起的發炎反應，並促進肝臟細胞的再生與抑制肝臟的凋亡。本實驗證明了MC能預防酒精所造成的肝臟損傷，並具有發展為保健食品的潛力。
並列摘要
Alcoholic hepatitis is a liver inflammation disease caused by excessive chronic alcoholism. In the mechanism of alcoholic hepatitis, ethanol is first oxidized by CYP2E1 (cytochrome P4502E1) and produce many reactive oxygen species (ROS), which exceed the antioxidant capacity, induces oxidation of proteins, lipids, and DNA, impair cellular functions, and trigger liver cell death. Myrciana cauliflora (MC), a low economic value crop, contains rich of anthocyanins which believed to have antioxidant activity, anti-inflammatory, anti-mutagenic effects and also can reduce lipid peroxidation and DNA damage. However, the anti-oxidatant and anti-inflammatory effects of MC in preventing alcoholic liver disease remain unknown. In this study, we evaluate the hepato-protective effect of MC in experimental alcoholic steatohepatitis animal models. After treatment with MC, low aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), and cholesterol were observed in the serum of alcohol-fed C57BL6/J mice. We then examine the lipid peroxidation in liver by using TBARS assay and determine some anti-oxidation enzymes and cytokines such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px). Lower level of lipid peroxidation anti-oxidation enzymes were found in MC-fed mice. Immunoblot analysis of proinflammatory cytokines such as NF-κB, TNF-α, IL-6, MCP-1, COX-2, iNOS and fatty acid synthesis-related protein such as sterol regulatory element-binding protein (SREBPs), fatty acid synthesis (FAS), acetyl CoA carboxylase (ACC) were reduced while MC was treated with alcohol-induced mice. At the meantime, MC also elevated the fatty acid oxidation-related protein such as peroxisome proliferator-activated receptor α (PPAR-α), carnitine palmitoyltransferase (CPT1), microsomal triglyceride transfer protein (MTP). It can also extenuate liver apoptosis and promote liver regeneration, indicating that MC can prevent the liver from alcohol-induced liver injury and provide well potential to develop new nutrition food.