臺灣博碩士論文加值系統

非酒精性脂肪肝病 (nonalcoholic fatty liver disease, NAFLD) 特徵為肝細胞中堆積大量脂肪，是臺灣地區常見的慢性肝臟疾病。許多民眾期望透過食品取代藥物達到預防或治療疾病的目的，因此市面上有許多保健食品可供選擇。難消化性麥芽糊精 (resistant maltodextrin, Fibersol-2) 為玉米澱粉以鹽酸加熱再以酵素水解而得，因不易被人體消化故常做為減重的健康素材。表沒食子兒茶素沒食子酸酯 (epigallocatechin gallate, EGCG) 為綠茶中含量最多的茶多酚，許多研究已證實綠茶具有降低血膽固醇及抗肥胖等功效。為了解兩者對於改善脂肪肝的影響，本次研究以雄性 Sprague-Dawley (SD) 品系大白鼠進行為期 15 週的動物實驗，所有組別共六組，分別為 (1) 正常控制組 (normal control, NC)、(2) 高脂飲食組 (high-fat diet, HF)、(3) 高脂飲食添加 0.2% Orlistat 組 (high-fat diet + 0.2% Orlistat, HO)、(4) 高脂飲食添加 5% Fibersol-2 組 (high-fat diet + 5% Fibersol-2, FS)、(5) 高脂飲食添加 1% EGCG 組 (high-fat diet + 1% EGCG, EG)、(6) 高脂飲食添加 5% Fibersol-2 及 1% EGCG 組 (high-fat diet + 5% Fibersol-2 + 1% EGCG, FE)。結果顯示高脂飲食添加 Fibersol-2 及 EGCG 後，肝臟中三酸甘油酯及總膽固醇濃度均顯著降低，並發現兩者皆可以透過誘導肝臟內 AMP-activated protein kinase (AMPK) 磷酸化蛋白表現量增加，進而抑制下游 acetyl-CoA carboxylase (ACC)、fatty acid synthase (FAS) 及 HMG-CoA reductase (HMGCR) 酵素活性，因此減少肝臟脂質堆積。當 HMGCR 活性下降導致肝臟總膽固醇濃度降低時，會刺激 sterol regulatory element binding proteins 2 (SREBP2) 表現量提升，使 low density lipoprotein receptor (LDLR) 表現增加而降低血漿中總膽固醇濃度。另外，Fibersol-2 及 EGCG 也能增加 peroxisome proliferator-activated receptor α (PPAR-α) 表現量，進一步提升 carnitine palmitoyl transferase 1α (CPT1-α) 及 uncoupling proteins 2 (UCP2) 之蛋白表現，以增加肝臟粒線體進行脂肪酸 β-oxidation。總體而言，高脂飲食添加 Fibersol-2 或 EGCG 可以提高肝臟 pAMPK 表現量，因此抑制肝臟脂質生合成酵素活性、刺激脂肪酸 β-oxidation 而改善脂肪肝，並降低血漿及肝臟中總膽固醇含量。然而，當兩者合併使用時並沒有顯著的協同作用。

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease, which is characterized by much lipid accumulation in liver cells. Many studies have shown that resistant maltodextrin (Fibersol-2) and epigallocatechin gallate (EGCG) have blood cholesterol lowering effect and anti-obesity. In order to investigate the effects of Fibersol-2 and EGCG on fatty liver, male Sprague-Dawley (SD) rats were fed with high-fat diet for 7 weeks. After then, rats were divided into 6 groups: (1) normal control (NC), (2) high-fat diet (HF), (3) high-fat diet + 0.2% Orlistat (HO), (4) high-fat diet + 5% Fibersol-2 (FS), (5) high-fat diet + 1% EGCG (EG), (6) high-fat diet + 5% Fibersol-2 + 1% EGCG (FE). The results showed that the levels of triglyceride and total cholesterol in liver were significantly decreased after Fibersol-2 and EGCG feeding. We found that both of them can reduce hepatic lipid accumulation through inducing AMP-activated protein kinase (AMPK) phosphorylation protein expression, which can inhibit the activities of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and HMG-CoA reductase (HMGCR). Meanwhile, HMGCR activity is inhibited to decrease hepatic cholesterol synthesis. This result stimulates sterol regulatory element binding proteins 2 (SREBP2) and low density lipoprotein receptor (LDLR) protein expressions thereby reducing cholesterol concentration in plasma. On the other hand, Fibersol-2 and EGCG can also increase β-oxidation of liver mitochondria by increasing the expressions of peroxisome proliferator activated receptor-α (PPAR-α), carnitine palmitoyl transferase 1α (CPT1-α) and uncoupling protein 2 (UCP2). Overall, high-fat diet with Fibersol-2 or EGCG can inhibit lipogenic enzyme activities and induce fatty acid β-oxidation through increasing pAMPK protein expression, thereby reducing the lipid accumulation in liver and cholesterol in plasma. However, the combination of Fibersol-2 and EGCG has no synergistic effect.

摘要 I
Abstract II
目錄 III
圖目錄 VI
表目錄 VII
詞彙縮寫表 1
第壹章、 前言 2
第貳章、 文獻整理 3
第一節 脂肪肝 (Fatty liver) 3
1. 定義 3
2. 致病機轉 3
3. 肝臟分泌 VLDL 作用 (VLDL secretion) 5
第二節 高脂飲食 (High fat diet) 6
1. 定義 6
2. 脂肪於體內之消化吸收 6
3. 飲食中添加膽固醇與脂質代謝之相關性 6
第三節 脂質代謝 (Lipid metabolism) 8
1. 脂肪組織 (Adipose tissue) 8
2. 脂肪細胞激素 8
3. 脂質代謝相關酵素 9
4. 基因蛋白 11
5. LDL receptor (LDLR) 13
6. Uncoupling proteins (UCPs) 14
7. AMPK (AMP-activated protein kinase) 15
第四節 難消化性麥芽糊精 (Resistant maltodextrin, RMD) 17
1. 難消化性麥芽糊精介紹 17
2. 難消化性麥芽糊精對脂質代謝之影響 18
3. 難消化性麥芽糊精之應用 18
第五節 Epigallocatechin gallate (EGCG) 19
1. 茶葉中的兒茶素 19
2. EGCG 對脂質代謝之影響 20
第六節 藥物介紹 21
1. Orlistat 21
2. Orlistat 對脂質代謝之影響 21
第參章、 實驗動機與目的 22
第肆章、 實驗設計 23
第一節 實驗流程 23
第二節 實驗材料 25
1. 實驗動物 25
2. 實驗飼料 25
3. 實驗樣品 25
4. 實驗儀器 25
第三節 實驗方法 27
1. 實驗分組 27
2. 動物飼養及樣品收集 27
3. 飼料配方 28
4. 樣品分析 29
5. 統計分析 42
第伍章、 結果 43
第一節 誘導期間大白鼠體重、血漿生化指標變化 43
第二節 實驗期間大白鼠體重、攝食量、食物利用率及飲水量變化 43
第三節 實驗犧牲後大白鼠組織臟器重量 43
第四節 犧牲後大白鼠血漿、脂肪組織及糞便之生化指標測定結果 44
1. 血漿脂質濃度變化 44
2. 血漿 AST、ALT 活性及尿酸濃度變化 44
3. 血漿發炎因子濃度變化 44
4. 血漿及肝臟脂質過氧化物濃度變化 44
5. 脂肪組織脂質濃度及脂肪相關激素測定結果 45
6. 糞便重量及脂質濃度測定結果 45
第五節 犧牲後大白鼠肝臟脂質濃度及脂質合成相關酵素測定結果 45
1. 肝臟脂質含量及合成相關酵素活性變化 45
2. 肝臟組織切片染色中脂肪空泡差異 45
第六節 犧牲後大白鼠血漿 adiponectin、GLP-1 濃度及肝臟 pAMPK/AMPK 之蛋白表現量測定結果 46
第七節 犧牲後大白鼠肝臟蛋白表現量測定結果 46
1. 肝臟 PPAR-γ 之蛋白表現量 46
2. 肝臟 PPAR-α及 CPT1-α之蛋白表現量 46
3. 肝臟 UCP2 之蛋白表現量 46
4. 肝臟 SREBP 2 及 LDL receptor 之蛋白表現量 46
第陸章、 討論 47
第一節 誘導期間高脂飲食對大白鼠體重及血液生化數值之影響 47
第二節 Fibersol-2 及 EGCG 對大白鼠體重及組織臟器之影響 47
第三節 Fibersol-2 及 EGCG 對大白鼠脂質代謝之影響 48
1. 對血漿脂質濃度之影響 48
2. 對脂肪組織脂質濃度之影響 48
3. 對糞便脂質濃度之影響 49
第四節 Fibersol-2 及 EGCG 對大白鼠肝腎功能之影響 49
第五節 Fibersol-2 及 EGCG 對大白鼠發炎因子濃度之影響 49
第六節 Fibersol-2 及 EGCG 如何改善大白鼠之脂肪肝 50
第柒章、 結論 52
第捌章、 參考文獻 54

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