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研究生: 王亮凱
Wang, Liang-Kai
論文名稱: 利用芝麻油降低硫代乙醯胺對肝臟傷害之研究
Effect of Sesame Oil against Thioacetamide-induced Hepatic Injury in Rats
指導教授: 劉明毅
Liu, Ming-Yie
學位類別: 碩士
Master
系所名稱: 醫學院 - 環境醫學研究所
Department of Environmental and Occupational Health
論文出版年: 2009
畢業學年度: 97
語文別: 中文
論文頁數: 71
中文關鍵詞: 硫代乙醯胺猛爆性肝衰竭氧化性壓力脂質過氧化作用骨髓過氧化酶芝麻油
外文關鍵詞: thioacetamide, fulminant hepatic failure, oxidative stress, lipid peroxidation, myeloperoxidase, sesame oil
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  • 先前的研究指出,急性肝傷害是造成多種肝病變的主要因素之一,可能部份由氧化性壓力而來,並進一步造成脂質過氧化作用產生傷害。在動物模式通常使用硫代乙醯胺來誘導急性且嚴重的肝傷害,以模擬猛爆性肝傷害的發生。芝麻油是由芝麻的種子中提煉而來,在過去的研究中指出,芝麻油被證實具有抗氧化性壓力與肝臟保護作用。本研究的目的在於:建立以芝麻油減緩在大鼠中以硫代乙醯胺所誘發的急性且嚴重的肝傷害。實驗中,先建立硫代乙醯胺之肝毒性劑量反應,並以實驗所得的有效傷害劑量做時間點試驗,找出適合的實驗時間點,以一次腹腔注射硫代乙醯胺(100 mg/kg)來誘導急性肝傷害,再利用芝麻油不同的劑量及次數來對抗硫代以醯胺所造成之肝傷害;灌食芝麻油後24小時犧牲動物,並取得血液與肝組織樣本以進行分析。結果由肝傷害指標-天門冬胺酸轉胺酶及丙胺酸轉胺酶的濃度高低發現,在24小時內(0, 6, 12小時)給予三劑芝麻油(4 ml/kg)能有效降低肝指數。血清與組織內之脂質過氧化產物丙二醛,具有顯著差異。另外骨髓過氧化酶活性上也達顯著性差異。因此,以多次芝麻油處理可明顯減輕硫代以醯胺所造成嚴重的肝傷害,但其保護作用可能透過降低大鼠肝臟中的骨髓過氧化酶活性,進而減少脂質過氧化作用發生。

    Introduction: Thioacetamide (TAA) is used to induce many acute hepatic injuries, such as fulminant hepatic failure (FHF) in animal models which relate to oxidative stress injuries. Many studies show that sesame oil (SO) protects liver through decrease oxidative stress and inflammation in acute animal models.
    Objective: To investigate the effect of SO on TAA-induced acute hepatic injury.
    Design: TAA (100 mg/kg; i.p) was used to induce acute hepatic injury. SO (1, 2, 4, and 8 ml/kg; orally) was administrated on different time points (0, 6, and 12h) after TAA injection. The serum and liver tissue samples were collected to analyze liver injuries on hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid peroxidation (LPO) level and inflammatory regulators such as myeloperoxidase (MPO), interleukin-6 (IL-6) and interleukin-10 (IL-10).
    Results: There was no significant difference between AST and ALT by using single dose of SO treatment. Double dose of SO treatments (0 and 12 h) with in 24 h also showed no significant difference on TAA-induced acute hepatic injury. However, the triple dose of SO treatments (0, 6, and 12 h) showed a significant decreased on AST and ALT with 4 ml/kg sesame oil, and the MDA level in liver also showed significant decreased. Also MPO activity was decreased after sesame oil treatment.
    Conclusion: SO attenuated TAA-induced acute hepatic injury significantly by using triple SO oral treatments. And the protection of SO was related with inhibition of MPO activity, furthermore, improved LPO injury.

    壹、研究背景 1 急性肝傷害(acute hepatic injury) 1 猛爆性肝衰竭 (fulminant hepatic failure) 2 硫代乙醯胺 (thioacetamide, TAA) 4 硫代乙醯胺在動物模式上的應用 4 氧化性壓力(oxidative stress)與脂質過氧化作用(lipid peroxidation) 5 一氧化氮(nitric oxide, NO) 7 骨髓過氧化酶(myeloperoxidase, MPO) 8 介白素-6 (interleukin-6, IL-6) 9 介白素-10 (interleukin-10, IL-10) 10 芝麻油(sesame oil, SO) 11 貳、研究目的 13 參、研究材料與方法 14 實驗動物 14 實驗藥品 14 實驗耗材 16 實驗儀器 17 實驗藥片及試劑組 18 分析軟體或繪圖軟體 18 實驗方法 21 測量項目 24 統計分析 29 肆、實驗結果 30 硫代乙醯胺與急性肝傷害之劑量反應關係 30 硫代乙醯胺與急性肝傷害之時間點 30 灌食芝麻油對硫代乙醯胺誘導的肝傷害之保護效果 (I) 31 灌食芝麻油對硫代乙醯胺誘導的肝傷害之保護效果 (II) 31 灌食芝麻油對硫代乙醯胺誘導的肝傷害之保護效果 (III) 31 兩次灌食芝麻油對硫代乙醯胺誘導的肝傷害之保護效果 32 三次灌食芝麻油對硫代乙醯胺誘導的肝傷害之保護效果 32 芝麻油對硫代乙醯胺所造成的脂質過氧化作用之影響 32 芝麻油對硫代乙醯胺在肝組織內所生成一氧化氮之影響 33 芝麻油對硫代乙醯胺在肝組織內所生成骨髓過氧化酶之活性影響 33 芝麻油對硫代乙醯胺在肝組織內所生成IL-6的影響 34 芝麻油對硫代乙醯胺在肝組織內所生成IL-10的影響 34 伍、實驗結果討論 36 陸、結論 40 柒、引用文獻 41 捌、圖表及附錄 52

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