| 研究生: |
陳文獻 Chen, Wen-Hsein |
|---|---|
| 論文名稱: |
動脈硬化老鼠出血性胃潰瘍及各種藥物保護作用之探討 Effects of Protective Drugs on Gastric Hemorrhagic Ulcers in Atherosclerotic Rats |
| 指導教授: |
洪正路
Hung, Chan-Lu |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 藥理學研究所 Department of Pharmacology |
| 論文出版年: | 2004 |
| 畢業學年度: | 92 |
| 語文別: | 中文 |
| 論文頁數: | 76 |
| 中文關鍵詞: | 胃酸逆擴散 、膽固醇 、動脈硬化 、胃緊迫性氧化 、脂質過氧化物 、出血性胃潰瘍 、升鈣醇 、麩胺基硫 、lysozyme 、lovastatin 、clofibrate 、verapamil |
| 外文關鍵詞: | cholesterol, acid back-diffusion, glutathione, gastric oxidative stress, calciferol, lipid peroxide, Hemorrhage ulcer, atherosclerosis |
| 相關次數: | 點閱:115 下載:2 |
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中文摘要
動脈硬化是心血管一種致命性疾病,而動脈硬化主要是因為血漿中膽固醇及低密度脂蛋白含量過高,受到自由基氧化,形成氧化態的脂質,進而內皮增生,粥狀動脈斑形成之現象。若能降低血漿中膽固醇及低密度脂蛋白含量及提高抗氧化能力,則可有效預防動脈硬化。鈣與膽固醇在動脈硬化的形成扮演很重要的角色,若同時給予升鈣醇與膽固醇能誘發大白鼠的動脈硬化。然而,對於這兩種物質的混合物是否能造成胃緊迫性氧化與黏膜的破壞則是未知的。本實驗的目的是研究由這種混合物所誘發的胃緊迫性氧化與黏膜傷害,以及評估數種藥物在這種潰瘍誘發模式的保護作用。雄性大白鼠每天餵食4.5mg/kg升鈣醇與22.5mg/kg膽固醇的蔬菜油,連續九天,而對照組只餵予蔬菜油。經過胃部手術之後,大白鼠胃部以人工胃液或生理食鹽水灌流,三小時之後將大白鼠犧牲。我們可以發現動脈硬化的大白鼠體內有胃酸逆擴散與黏膜脂質過氧化物的增高,出血性潰瘍面積的增加與黏膜麩氨基硫的減少,也發現胃黏膜脂質過氧化物含量與潰瘍面積成正相關。在動脈硬化實驗組發現,若每天以餵食器經口直接投予大白鼠胃部下述藥物及劑量: clofibrate(300mg/kg),verapamil (20mg/kg)或是lovastatin (10mg/kg), lysozyme(500mg/kg) 都可以有效地保護胃黏膜。綜合以上的觀察,升鈣醇與膽固醇的混合物會造成胃緊迫性氧化,這在動脈硬化大白鼠形成出血性胃潰瘍扮演很重要的角色。
Abstract
Calcium and cholesterol play an important role in the formation of atherosclerosis. Feeding the mixture of calciferol and cholesterol induces the atherosclerosis in rats. This atherosclerotic aorta was characterized by medial calcification and intimal cell proliferation. However, it is unknown whether the mixture of cholesterol and calciferol also causes gastric hemorrhage and mucosal damage. The aim of our study is observing the gastric oxidative stress and mucosal damage induced by the mixture of calciferol and cholesterol, and we evaluated the protective effects of several drugs. The effects of these drugs were significantly attenuated in the VD+CHOL as compared with the control. Male Wistar rats were challenged intragastrically with 1ml vegetable oil containing calciferol (4.5mg/kg) and cholesterol (22.5mg/kg), once daily and for 9 days. We fed normal rats with vegetable oil alone. During gastric surgery, rat stomachs were irrigated with physiological acid solution or normal saline for 3hrs. After that rats were sacrificed. We observed the increased level of acid back-diffusion, mucosal lipid peroxide content and hemorrhage ulcer area, and the decreased mucosal glutathione content in atherosclerotic rats. Besides, there was a high correlation between mucosal lipid peroxide levels and ulcer areas. Daily feeding clofibrate (300mg/kg), verapamil (20mg/kg), lovastatin (10mg/kg) or lysozyme (500mg/kg) effectively protected gastric mucosa in atherosclerotic rats. In conclusion, the mixture of calciferol and cholesterol may be produced gastric oxidative stress, which is an important factor in the formation of hemorrhagic ulcer in atherosclerotic rats.
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