臺灣博碩士論文加值系統

摘 要

氧化壓力與發炎反應是影響致粥狀最重要的因素與促進者，由於影響血管內皮黏附分子的表現，在動脈粥狀硬化形成和慢性發炎中扮演重要角色。許多研究顯示膳食補充大豆食品可降低心血管疾病，尤其是黑豆富含的異黃酮素包括染料木黃酮(genistein)、二羥異黃酮(daidzein)，並且在其種子外皮富含矢車菊色素配質(cyanidin)，而其所具有良好的抗氧化物質是否能在細胞內調控對活性氧敏感性的訊息傳遞路徑之基因表現，進而影響黏附分子的表現與致粥狀的發展。是以本研究主要探討黑豆萃取物及其主成分 genistein、 daidzein 和 cyanidin 對前發炎細胞激素腫瘤壞死因子（TNF-α）誘導人類主動脈內皮細胞(human aortic endothelial cells；HAEC)發炎反應的影響。首先以 MTT檢測樣品對 HAEC的影響，結果顯示黑豆萃取物在 200 μg/mL濃度以下及 genistein、daidzein 和 cyanidin各分別在 40、40、20 μM濃度以下對 HAEC 不具細胞毒性；將 HAEC預先以 100 μg/mL黑豆萃取物及 10 μM genistein、daidzein、cyanidin和 aspirin處理 18小時，可顯著降低人類單核球細胞株-U937 與 HAEC間的黏附性，其抑制率依序為 98.2%、97.2%、98.8%、93.1% 和 90.9%；利用細胞酵素連結免疫分析法顯示：genistein與對照組 aspirin可明顯降低細胞間黏附分子（ICAM-1）表現分別達 17.1% 和 14.5%；黑豆萃取物及 genistein、daidzein、cyanidin、aspirin亦可顯著降低血管黏附分子（VCAM-1）表現依序達 47%、56.8%、59%、38.9% 和 42.7%；而對 E-selectin的表現則不具影響。經由 10%聚丙烯醯胺膠體電泳分析和西方墨點法分析，黑豆萃取物，可顯著降低腫瘤壞死因子所引起 NF-κB p65的表現。綜合研究顯示黑豆萃取物及其主要成分有助於減緩發炎反應及動脈粥狀硬化的進展。

Abstract

Oxidative stress and inflammation are thought to be an important contributor and promoter of atherogenesis. While altered expression of cell adhesion molecules by the arterial endothelium plays a major role during atherogenesis and chronic inflammation.
Several studies have demonstrated that the dietary intakes of soy foods were associated with reduction of cardiovascular risk. Interestingly, black soybeans rich in isoflavones (genistein and daidzein), and its seed coat contains cyanidin. Antioxidants may modulate of oxidative stress which may trigger intracellular signaling pathways influencing gene and adhesion molecules expression and atherogenesis. We determined the potential anti-atherogenic activity of black soybeans extract and its components by examining their effects on monocytes adhesion of human aortic endothelial cells (HAEC), adhesion molecules expression, and NF-κB-p65 expression. The black soybean extract (less than 200 μg/mL) and its components such as genistein, daidzein and cyanidin (less than 40, 40 and 20 μM, respectively) had no toxicity to HAEC. Pre-incubated of HAEC with 100 μg/mL black soybean extract and 10μM of genistein, daidzein, cyanidin and aspirin for 24h, significantly decreased adhesion of U937 monocytic cells to TNF-α-stimulated HAEC by 98.2%, 97.2%, 98.8%, 93.1% and 90.9%, respectively. Ten micromoles of genistein, daidzein, cyanidin and aspirin significantly suppressed the expression of vascular cell adhesion molecule-1(VCAM-1) by 47%, 56.8%, 59%, 38.9% and 42.7%, respectively. Genistein and aspirin significantly decreased intracellular adhesion molecule-1(ICAM-1) expression by 7.1% and 14.5% while all treatments had no effect on E-selectin. Pretreated black soybean extract could significantly inhibited NF-κB-p65 activaty in TNF-α-stimulated HAEC was assayed by SDS-PAGE and western blot. In conclusion, black soybean and its components may have potential on anti-inflammatory and anti-atherogenesis.

目錄
頁次
中文摘要 Ι
英文摘要 Ⅲ
致謝 Ⅴ
目錄 Ⅵ
縮寫表 Ⅸ
表目錄 ⅩⅡ
圖目錄 ⅩⅢ
附表目錄 ⅩⅤ
附圖目錄 ⅩⅥ
壹、緒言 1
貳、文獻回顧 3
一、 黑豆及其主要成分之生理機能 3
(一) 黑豆介紹 3
(二) 黑豆的生理機能 5
二、異黃酮 7
(一) 異黃酮生理代謝 9
(二) 異黃酮的生理活性 10
三、花青素 15
(一) 花青素介紹 15
(二) 花青素之生理活性 17
四、動脈粥狀硬化之簡介 19
(一) 動脈硬化的致病機轉 21
(二) 動脈硬化與腫瘤壞死因子的相關性 27
(三) 動脈硬化與細胞表面黏附分子之相關性 33
(四) 動脈硬化與轉錄因子的相關性 40
(五)動脈硬化與氧化壓力之相關性 45
叁、實驗材料與方法 48
一、實驗設計與架構 48
二、實驗目的 49
三、實驗儀器設備 50
四、材料與方法(分為二部份) 51
第一部份 黑豆成分之高效能液相層析儀分析 51
(一) 異黃酮素之定性及定量 51
(二) 矢車菊色素配質之定性和定量 56
第二部分 細胞試驗 58
一、實驗材料 58
二、實驗方法 63
(一) 人類主動脈內皮細胞株之培養 63
(二) 人類單核球細胞培養 64
(三) 細胞存活率測定 65
(四) 內皮細胞/單核球細胞粘附試驗 67
(五) 細胞表面黏附分子的測定 68
(六) 蛋白質活性之分析 69
三、統計方法 73
肆、結果與討論 74
伍、結論 89
陸、參考文獻 104
全文完

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