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系統識別號 U0007-2407201715395200
論文名稱(中文) 飲食中不同油脂合併補充枸杞多醣萃取物對四氯化碳誘發肝纖維化大鼠之影響
論文名稱(英文) Effects of different dietary oils combined with Lycium barbarum polysaccharide extract on liver fibrosis induced by CCl4 in rats
校院名稱 臺北醫學大學
系所名稱(中) 保健營養學研究所
系所名稱(英) Graduate Institute of Nutrition and Health
學年度 105
學期 2
出版年 106
研究生(中文) 江昀芸
研究生(英文) Yun-Yun Chiang
學號 M507104017
學位類別 碩士
語文別 中文
口試日期 2017-06-13
論文頁數 95頁
口試委員 指導教授-趙振瑞
委員-蔡英傑
委員-楊素卿
中文關鍵字 橄欖油  枸杞多醣體  細胞凋亡  發炎反應  肝纖維化 
英文關鍵字 olive oil  Lycium barbarum polysaccharides  apoptosis  inflammation  liver fibrosis 
學科別分類
中文摘要 目前肝纖維化還未有有效的治療方式,而先前研究指出,橄欖油與枸杞多醣體皆具有保護肝臟的作用,本次實驗欲探討飲食中不同油脂合併枸杞多醣萃取物(Lycium barbarum polysaccharide extract, LBE)補充,對於四氯化碳(carbon tetrachloride, CCl4)誘發肝纖維化大鼠之發炎反應、細胞凋亡及纖維化的影響。雄性Sprague-Dawley 大鼠隨機分成七組:正常飲食組(4%大豆油飲食)、大豆油飲食組(4%大豆油飲食+ CCl4)、橄欖油飲食組(4%橄欖油飲食+ CCl4)、大豆油/橄欖油飲食組(2%大豆油/2%橄欖油飲食+ CCl4)、大豆油飲食+ LBE組(4%大豆油+ LBE + CCl4)、橄欖油飲食+LBE組(4%橄欖油+ LBE + CCl4)、大豆油/橄欖油飲食+ LBE組(2%大豆油/2%橄欖油飲食+ LBE + CCl4)。LBE給予量為每天50 mg/kg bw,預先給予油脂或/和LBE一週後,每週腹腔注射1-2 mL/kg bw誘發肝纖維化,共注射八週。結果顯示注射四氯化碳之六組有較嚴重的肝臟脂質堆積、細胞死亡、發炎反應及纖維增生,含有橄欖油的飲食可降低肝臟TGF-β1與TIMP-1濃度;給予LBE可降低肝臟caspase-9與caspase-3活性,降低肝臟TNF-α濃度,增加IL-10/TNF-α比值,降低肝臟TGF-β1與TIMP-1濃度;當橄欖油與LBE合併給予,可降低肝臟caspase-9與caspase-3活性、降低肝臟TNF-α濃度,增加肝臟IL-10濃度與IL-10/TNF-α比值,降低肝臟TGF-β1與hydroxyproline濃度。對於注射四氯化碳8週之大鼠,枸杞多醣萃取物可改善細胞凋亡、發炎反應及纖維化指標,而橄欖油合併枸杞多醣萃取物的改善效果更佳。
英文摘要 The effective therapy for liver fibrosis is still elusive. Olive oil and Lycium barbarum polysaccharides were considered to act as hepatoprotective activity. This study investigated anti-inflammatory, anti-apoptosis and anti-fibrotic effects of different dietary oils and Lycium barbarum polysaccharide extract (LBE) on CCl4-induced liver fibrosis in rats. Male Sprague-Dawley rats were divided into 7 groups: normal diet (4% soybean oil diet), soybean oil diet (4% soybean oil diet + CCl4), olive oil diet (4% olive oil diet + CCl4), soybean oil/olive oil diet (2% soybean oil / 2% olive oil diet + CCl4), soybean oil diet + LBE (4% soybean oil diet + LBE + CCl4), olive oil diet + LBE (4% olive oil diet + LBE + CCl4), and soybean oil/olive oil diet + LBE (2% soybean oil / 2% olive oil diet + LBE + CCl4). The LBE-treated groups were given 50 mg/kg/day LBE. Rats were injected with 1-2 ml/kg bw/wk CCl4 intraperitoneally for 8 weeks. The results showed that CCl4 caused more severe liver fatty change, cell death, inflammation, and collagen generation. The groups treated with olive oil reduced hepatic TGF-β1 and TIMP-1 concentrations. LBE reduced hepatic caspaspe-3 and caspase-9 activities, decreased the hepatic TNF-α level, increased IL-10/TNF-α ratio, and reduced hepatic TGF-β1 and TIMP-1 concentrations. The groups treated with olive oil combined with LBE reduced hepatic caspaspe-3 and caspase-9 activities, decreased hepatic TNF-α level, increased hepatic IL-10 level and IL-10/TNF-α ratio, as well as reduced hepatic TGF-β1 and hydroxyproline concentrations. Therefore, after CCl4 injection for 8 weeks in rats, LBE improves apoptotic, inflammatory and fibrotic markers, while olive oil combined with LBE has better effects on anti-apoptosis, anti-inflammation and anti-fibrosis.
論文目次 中文摘要 I
Abstract II
致謝 III
目錄 IV
圖目次 VI
表目次 VII
第一章 緒論 1
第二章 文獻回顧 5
第一節 肝臟功能與結構 5
第二節 肝臟纖維化之成因與演進 7
第三節 四氯化碳誘發肝纖維化之動物模式 10
一、 四氯化碳造成肝損傷之機制 10
二、 四氯化碳與細胞凋亡指標 12
三、 四氯化碳與發炎反應指標 12
四、 四氯化碳與肝纖維化指標 14
第四節 飲食中油脂成分對肝臟疾病之影響 18
一、 飲食中油脂成分對肝臟脂質代謝的影響 18
二、 橄欖油對肝臟纖維化的影響 20
第五節 枸杞多醣體對肝臟疾病之影響 21
一、 枸杞多醣體簡介 21
二、 枸杞多醣體之肝臟相關研究 23
第六節 研究目的與動機 25
第三章 實驗材料與方法 26
第一節 實驗設計 26
一、 實驗動物 26
二、 實驗設計 26
三、 飲食中的油脂 29
四、 枸杞多醣萃取物 32
第二節 測定項目與方法 35
一、 肝臟切片 35
二、 肝功能指標 36
三、 血漿與肝臟脂質濃度 37
四、 肝臟細胞凋亡指標 40
五、 肝臟發炎反應指標 41
六、 肝臟纖維化指標 43
第三節 統計分析 47
第四章 結果 48
第一節 大鼠體重、肝重與攝食量 48
第二節 肝功能指標 50
第三節 血漿與肝臟脂質成分 52
第四節 肝臟切片病理學檢查 54
第五節 肝臟細胞凋亡指標 58
第六節 肝臟發炎指標 60
第七節 肝臟纖維化指標 63
第五章 討論 69
第一節 以CCl4動物模式模擬人體之肝纖維化 69
第二節 CCl4對肝重與肝功能之影響 71
第三節 CCl4對脂質代謝之影響 72
第四節 橄欖油對肝臟細胞凋亡與發炎反應的影響 74
第五節 LBE對肝臟細胞凋亡與發炎反應的影響 76
第六節 橄欖油與LBE對肝臟纖維化指標的影響 78
第七節 綜合討論 83
第六章 結論 87
第七章 參考資料 88
附件一 實驗動物照護及使用委員會審查同意書 95
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