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系統識別號 U0026-2008201517161500
論文名稱(中文) 芝麻油對酮康唑誘發肝臟傷害之影響
論文名稱(英文) Effects of sesame oil on ketoconazole-induced hepatic injury in mice
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 103
學期 2
出版年 104
研究生(中文) 陳瑩倩
研究生(英文) Ying-Chien Chen
學號 S76011091
學位類別 碩士
語文別 中文
論文頁數 51頁
口試委員 指導教授-劉明毅
口試委員-張志欽
口試委員-吳致杰
口試委員-許德榮
中文關鍵字 酮康唑  肝臟傷害  氧化壓力  細胞凋亡  芝麻油 
英文關鍵字 ketoconazole  hepatic injury  oxidative stress  apoptosis  sesame oil 
學科別分類
中文摘要 酮康唑為一咪唑類的抗黴菌藥物,在過去常被用來治療黴菌感染,然而隨著酮康唑廣泛地使用,口服酮康唑對於肝臟有相當的風險性,造成肝臟發炎或壞死等傷害,目前對於酮康唑所造成的肝臟毒性並沒有有效的治療方法,只能經由定期檢查以及控制用藥等方式來預防。過去研究發現酮康唑透過增加脂質過氧化反應以及DNA片斷化來造成肝臟傷害,因此氧化壓力在酮康唑誘導的肝臟傷害中扮演相當重要的角色。芝麻油為芝麻種子提煉出的一種油脂具高度的穩定性,芝麻油中富含豐富的木質素、維生素E等抗氧化物質可降低氧化壓力,在許多氧化壓力相關的肝臟傷害模式中,芝麻油能透過降低氧化壓力,達到減緩肝臟傷害的作用,且能夠有效地降低細胞凋亡的作用;然而芝麻油對於酮康唑誘導的肝臟傷害之作用還未被探討過,因此本研究目的為探討芝麻油對於酮康唑誘導的肝臟傷害之作用及可能的作用機制。每日以灌食方式給予老鼠酮康唑(300 mg/kg),三十分鐘後,給予不同劑量的芝麻油(0.0625, 0.125, 0.25, 0.5 ml/kg),連續給予14天,實驗結束後,以血液中肝功能指標、肝臟組織切片、細胞色素p450、骨橋蛋白表現標評估老鼠肝臟損傷的情況;分析肝臟中p53、Bcl-2、caspase3蛋白的表現量,評估細胞凋亡情形;以肝臟中脂質過氧化程度作為氧化壓力指標,並量測肝臟中一氧化氮、超氧陰離子、過氧化亞硝酸基、羥基生成以及抗氧化物榖胱甘肽之含量;以量測骨髓過氧化酶表現評估嗜中性球細胞的活化情形。結果顯示,芝麻油能有效減緩14天連續給予酮康唑誘導老鼠肝臟損傷,降低肝臟中自由基的生成以及脂質過氧化反應、維持榖胱甘肽的表現量、減緩細胞凋亡。總之,本研究推測芝麻油透過降低嗜中性球細胞的活化,抑制氧化壓力誘導的細胞凋亡路徑,達到保護肝臟的作用。
英文摘要 Ketoconazole is one of the most commonly used systemic antifungal drugs. However, long-term treatment of ketoconazole causes hepatic injury in patients. Oxidative stress and its related apoptosis are involved in ketoconazole-induced hepatic injury. Sesame oil is edible oil derived from sesame seeds rich with potent antioxidants. It protects against oxidative stress-associated hepatic injury in various models. However, the effect of sesame oil on ketoconazole-induced hepatic injury has never been investigated. The aim of the study was to investigate the protective effect of sesame oil on ketoconazole-induced hepatic injury in mice. Ketoconazole (300 mg/kg/day, p.o.) was given 30 min after sesame oil (0.25 or 0.5 ml/kg/day, p.o.) to ICR mice for 14 days. Blood and liver tissue were collected. Neutrophil activation was determined by myeloperoxidase activity. Free radicals, lipid peroxidation, and glutathione were measured to assess oxidative stress. Apoptosis was evaluated by p53, bcl-2, and caspase3 expression. Hepatic injury was evaluated by p450 expression, serum biochemistry, histology, and osteopontin level. Sesame oil inhibited caspase3 and p53, but increased bcl-2 compared with ketoconazole-treated mice. Further, sesame oil inhibited lipid-peroxidation, increased glutathione, and inhibited myeloperoxidase activity in ketoconazole-treated mice. Sesame oil maintained cytochrome p450 expression, inhibited osteopontin level, and inhibited serum AST and ALT in ketoconazole-treated mice. In conclusion, sesame oil might protect against ketoconazole-induced hepatic injury by inhibiting neutrophil activation thereby decreased oxidative stress-associated apoptosis in mice.
論文目次 中文摘要 I
英文摘要 II
誌謝 X
目錄 XII
圖目錄 XIII
研究背景 1
研究材料與方法 10
實驗結果 19
實驗結果討論 22
研究結論 26
參考文獻 27
附錄 49
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