| Abstract: | 根據文獻以及統計數上顯示，高血脂症、糖尿病、肥胖、肝炎、心血管疾病經常伴隨肝臟大量堆積脂肪的病狀，正常人類肝臟組織含有少量脂肪如甘油三脂、磷脂、醣脂以及膽固醇，其重量約為肝重量的4~5 %，肝臟內脂肪含量超過肝重量5 %以上，或以肝組織切片診斷肝細胞含有脂肪空泡堆積超過肝重量10 %以上，即所謂脂肪肝。雖然脂肪肝沒有太明顯的病狀，若進一步造成脂肪性肝炎則會導致一連串病變，肝臟的纖維化與肝硬化，進而促進肝癌的形成。本計畫擬以細胞實驗及動物試驗進行評估，以油酸處理肝細胞，利用nile red染色觀察脂肪滴形成，並以動物實驗餵食高脂肪食物誘導脂肪肝，細胞及動物血清、肝臟組織分析TG、TC、HDL-C及LDL-C，進一步分析肝臟fatty acid synthase活性，再以Western blotting及RT-PCR分析FAS、HMG-CoA reductase、Glycerol-3-acyltrasferase、HMG-CoA reductase、LDL-R、及PPAR-α等與排除肝臟脂肪相關蛋白。 由於本實驗室已證實桑椹萃取物是具有抑制脂肪肝之作用，且在本實驗室近年研究也發現桑椹萃取物具有排除肝臟脂肪之效用，我們進一步利用肝細胞及動物實驗模式來建立保健食品是否能作為預防或延緩罹患脂肪肝之評估方法。並以桑椹萃取物及臨床藥物statin證實其在減緩脂肪肝行程評估模式之可行性。 研究成果顯示，利用油酸處理肝細胞之細胞模式及高脂肪餵食動物之模式可用來評估健康食品減緩脂肪肝行程之方法，進一步可利用抑制脂肪合成及促進脂肪代謝確認健康食品之作用。
Base on the data of literatures and epidemiological statistics, abundant lipid accumulation usually appears in hyperlipidemia, diabetes, obesity, hepatitis and cardiovascular diseases. In normal liver tissue, little lipid such as triglyceride, phospholipid, glycolipid and cholesterol existing in body is equal to 4-5% of whole liver weight. Since lipid content up to 5% of liver weight or sterosis up to 10% of liver weight in biopsy diagnosis is so-called fatty liver. Although fatty liver without dominate symptoms, the progression would further cause fatty hepatitis, liver fibrosis, liver cirrhosis or promoting hepatoma formation. In the study, we want to evaluate fatty liver in in vitro and in vivo. Firstly, hepatocytes will be treated with oleic acid to observe the lipoid by using Nile red O stain. Secondly, animals will be fed high lipid diet to induce fatty liver. The samples from hepatocytes, serum and liver tissues will be analyzed several parameters such as triglyceride, total cholesterol, HDL-C and LDL-C. In the other hand, for mechanism investigation on excluding lipid in liver, we will further detect liver fatty acid synthase, activity, expressions of FAS, HMG-CoA reductase, Glycerol-3-acyltrasferase, HMG-CoA reductase, LDL-R, and PPAR-α. In our previous study, we have proved mulberry extract possessing the ability to inhibit fatty liver and also exclude the lipid accumulating in liver. Herein, we want to setup a series of evaluating methods for health caring foods on preventing or decelerating fatty liver. Furthermore, we will also use mulberry extract comparing with statin to prove the possibility on lowering fatty liver. In our studies, the results showed that cells treated with oleic acid and animals fed with high fat diet as the model to attenuate hepatic lipid accumulation, and evaluated the methods for heath caring foods on preventing fatty liver. Forthermore, we will investigate the lipogenesis inhibitors and promoting catabolism by down regulation the activity of key enzymes of metabolism to comfirm the effect of heath caring foods. |
