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研究生:李美玲
研究生(外文):Mei-Ling Li
論文名稱:高分子原兒茶酸聚合物活化轉錄因子NF-κB及誘導動脈粥狀硬化機制探討
論文名稱(外文):High Molecular Protocatechuic Acid Polymers Induces Atherosclerosis and NF-κB Activation
指導教授:楊新玲楊新玲引用關係
指導教授(外文):Hsin-Ling Yang
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:營養學系碩士班
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:126
中文關鍵詞:高分子原兒茶酸烏腳病動脈粥狀硬化NF-κB
外文關鍵詞:High molecular Protocatechuic acid polymerBlackfoot diseaseAtherosclerosisNuclear factor-kappa B
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高分子原兒茶酸(腐植酸)已被證實為台灣西南沿海烏腳病的致病因子之ㄧ。在本篇研究中,我們探討腐植酸誘導動脈粥狀硬化及活化轉錄因子NF-κB之機制。在動物實驗結果發現,腐植酸可以誘導動脈粥狀硬化的發生,而此情形並不是經由增加血漿中的膽固醇及三酸甘油脂。在體外試驗中發現,腐植酸會(1)促進人類臍帶內皮細胞黏附因子(例如:ICAM-1、VCAM-1)以及COX-2蛋白質表現;(2)促進鼠類巨噬細胞RAW 264.7細胞株COX-2、iNOS、L-1β、TNF-α、PGE2 以及NO的釋放;(3)並會促進A7r5大鼠平滑肌細胞株MMP-9、PDGF-A以及COX-2蛋白質表現。而NF-κB訊息傳遞路徑在這些表現的機制上扮演重要的角色。因此我們可以知道,腐植酸會促進烏腳病患者的動脈粥狀硬化發生,在此其中NF-κB為此疾病病因發生的主要因子之ㄧ。
High molecular Protocatechuic acid polymer (humic acid, HA) have been implicated as an etiological factor of Blackfoot disease (BFD) endemic in the southwest coast of Taiwan. In this study, we investigated the effect of HA on atherosclerosis and activation of nuclear factor – kappa B (NF-κB). In animal study, we suggest HA can increase the atherosclerosis. This increase was not due to increasing in serum cholesterol and triacylglycerol (TG). In vitro study, HA was shown to enhance (1) activation of adhesion molecular (ex: intercellular cell adhesion molecule-1, ICAM-1; vascular cell adhesion molecule-1, VCAM-1) and COX-2 in human umbilical vein endothelial cells; (2) expression of cyclooxygenase-2 (COX-2), induce nutric oxide synthase (iNOS), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and nutric oxide (NO) in RAW264.7 macrophage cell line; (3) activation of matrix metalloproteinase (MMP-9), platelet derived growth factor-A (PDGF-A), and COX-2 in A7r5 rat smooth muscle cell line. NF-κB signal pathway play an important role in the mechanism. In conclusion, HA may increase the atherosclerosis, occurs for patients with blackfoot disease, NF-κB may be a critical molecular in the pathogenesis of this disease.
前言----------------------------------------------- 5
實驗目的----------------------------------------- 30
實驗方法 ---------------------------------------- 31
動物實驗部份結果與討論--------------------- 57
細胞實驗部份結果與討論
1.腐植酸對於人類臍帶靜脈內皮細胞之影響--------- 65
2.腐植酸對於小鼠巨噬細胞株RAW 264.7之影響-- 77
3.腐植酸對於A7r5大鼠平滑肌細株胞之影響-------- 92
結論------------------------------------------------- 101
參考資料-------------------------------------------104
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