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研究生:趙紫宇
研究生(外文):Tzu-Yu Chao
論文名稱:百里香酚降低高血脂兔子氧化壓力與發炎相關基因之表現
論文名稱(外文):Thymol reduces oxidative stress and inflammatory-related gene expression in hyperlipidemic rabbits
指導教授:余雅美
指導教授(外文):Ya-Mei Yu
學位類別:碩士
校院名稱:長榮大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:63
中文關鍵詞:動脈粥樣硬化百里香酚血脂發炎相關的基因高脂血症兔
外文關鍵詞:AtherosclerosisThymolBlood lipidsInflammatory - related geneHyperlipidemic rabbits
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  • 被引用被引用:1
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心血管疾病(CVD)在台灣是主要的死亡原因之一,最新的統計顯示,十大死因中腦血管疾病和心臟疾病分別為第二位及第四位。許多研究顯示,動脈粥狀硬化在心血管疾病的發展中扮演重要角色,也是導致心臟、腦血管疾病的主要原因。在台灣百里香的葉子是烹調常用的香料之一。百里香酚(Thymol)為百里香所含有之主要的多酚類,研究顯示百里香具抗氧化、抗發炎能力。本研究以高油高膽固醇飲食誘發紐西蘭白兔動脈粥狀硬化之研究模式,目的為探討百里香酚抗氧化與改善粥狀動脈硬化的形成之效果。本研究使用二十四隻紐西蘭大白兔,實驗期間隨機分配成四組,並於八週後犧牲;正常飲食組(N),高油高膽固醇飲食組(HC;添加10%豬油與1%膽固醇),百里香酚T3 實驗組(高油高膽固醇飲食再添加3 mg/kg/day 百里香酚),百里香酚T6實驗組(高油高膽固醇飲食再添加6 mg/kg/day 百里香酚)。實驗結果顯示實驗組與高油高膽固醇飲食組(HC)相比百里香酚可以降低血清中總膽固醇(TC)、三酸甘油酯(TG) 、低密度脂蛋白膽固醇(LDL-C) 、丙二醛(MDA) 、C-反應蛋白(CRP)與內膜增厚之情形。百里香酚與高油高膽固醇飲食組(HC)相比可以增加高密度脂蛋白膽固醇(HDL-C) 與總抗氧化狀態(TAS)。除此之外利用real time PCR 來計算mRNA 表現量。百里香酚可以降低基質金屬蛋白?-9 (MMP-9)、血管細胞黏附蛋白-1 (VCAM-1)、單核細胞趨化蛋白-1 (MCP-1)、介白素-6 (IL-6)、介白素-1 (IL-1Β)、腫瘤壞死因子-α (TNF-α)、腫瘤壞死因子-β (TNF-β)的基因表現。因而推論百里香酚可以降低高血脂症之兔子的血脂質、減少氧化壓力與發炎相關基因之表現,進而降低動脈粥狀硬化的發展。

Cardiovascular disease (CVD) is one of the major causes of death in Taiwan. Previous studies indicated that atherosclerosis might play a key role in the development of CVD. Thyme is one of the cooking spices commonly used in Taiwan. Thymol is major polyphemlic conrpond in the thyme, it has antioxidantive ability. The aim of this study is to examine the effects of thymol on oxidative stress, aorta ROS production and the gene expression of inflammatory markers in hyperlipidemia rabbits. Twenty-four New Zealand White (NZW) male rabbits were assigned randomly into four dietary groups and were scarified after eight weeks. The normal group was fed with regular rabbit chow and the HC group (hight cholesterol diet ; HC) was fed with a high fat and cholesterol diet with 10% lard and 1% cholesterol for 8 weeks. The thymol groups were fed with the same diet as the HC group plus 3 mg/kg/day of thymol (T3 group) or 6 mg/kg/day of thymol (T6 group) for 8 weeks. The serum levels of total cholesterol, triglyceride, LDL-cholesterol, Malondialdehyde (MDA), C-reactive protein (CRP), and intimal thickening was significantly increased in the HC group compared with the normal group, and decreased in the T3 and T6 groups compared with the HC group. The serum levels of HDL-cholesterol and total antioxidant status (TAS) were significantly increased in the T6 group compared with the HC group and T3 group. The mRNA expression of MMP-9 (Matrix Metalloproteinase 9), VCAM-1 (vascular cell adhesion protein 1), MCP-1 (ponocyte chemotactic protein-1), IL-6 (interleukin-6), IL-1β (interleukin-1), TNF-α (tumor necrosis factor-α) and TNF-β (tumor necrosis factor-β) was significantly increased in the HC group compared with the normal group, and decreased in the T3 and T6 group by real time PCR assay. In conclusion, our results indicated that thymol suppressed the progression of atherosclerosis by lowering serum lipid, reducing oxidative stress and inflammatory-related gene expression in hyperlipidemic rabbits.

Contents
Table and figure of contents in Introduction ............................................ v
Table and figure of contents in Results .................................................. vi
Abbreviation ......................................................................................... viii
摘要 ....................................................................................................... x
Abstract .................................................................................................. xii
I. Introduction......................................................................................... 1
1. Cardiovascular disease .................................................................. 1
2. Oxidative stress and atherosclerosis ............................................. 2
3. Inflammation and atherosclerosis ................................................. 4
4. The correlation of the acute response protein (CRP) and
atherosclerosis ............................................................................... 7
5. MMP (Matrix metalloproteinases) and atherosclerosis ................ 8
6. Thyme............................................................................................ 9
II. Research ideas .................................................................................. 17
III. Materials and methods ...................................................................... 17
(I) Materials ...................................................................................... 17
1. Medicines .................................................................................... 17
2. Apparatus .................................................................................... 18
(II) Methods ....................................................................................... 18
1. 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. ....................................................................................... 18
2. The total antioxidant capacity ..................................................... 19
3. Animal experiments .................................................................... 19
4. Biochemical studies .................................................................... 20
5. Measurement of serum MDA level ............................................. 20
6. Morphological studies ................................................................. 21
7. RNA isolation and Real time-PCR ............................................. 21
8. Statistical analysis ....................................................................... 22
IV. Results ............................................................................................... 25
1. Antioxidative capacity of thymol in vitro ................................... 25
2. Body weight and food intake ...................................................... 25
3. Blood biochemical Data .............................................................. 25
4. Plasma levels of TBAR ............................................................... 26
5. Serum levels of total antioxidative capacity (TAS) and C-reactive
protein (CRP) after supplementation with Thymol .................... 26
6. Morphology change of the tissue aortic arch .............................. 26
7. mRNA expression of inflammation-related gene ....................... 27
V. Discussion ......................................................................................... 42
VI. Conclusion ........................................................................................ 48
VII.References ........................................................................................ 49


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