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| Title: | 3,5,6,7,8,3 ,4 -heptamethoxyflavone及5-hydroxy- 3,6,7,8,3 ,4 -hexamethoxyflavone對脂泡細胞形成及脂質衡定之影響
Citrus flavonoid, 3,5,6,7,8,3 ,4 -heptamethoxyflavone and 5-hydroxy- 3,6,7,8,3 ,4 -hexamethoxyflavone suppress foam cell formation in THP-1 cells and alter lipid homeostasis in HepG2 liver cells |
| Authors: | 傅士航 |
| Contributors: | 嘉南藥理科技大學：生物科技系暨研究所
吳明娟 |
| Keywords: | 脂泡細胞形成
多甲氧基類黃酮
THP-1
CD36
HepG2
foam cell formation
polymethoxylated flavone
THP-1
CD36
HepG2 |
| Date: | 2011 |
| Issue Date: | 2011-10-25 15:30:04 (UTC+8) |
| Abstract: | 本論文的目的為探討柑橘皮的兩種結構相關的多甲氧基類黃酮 (PMFs, polymethoxylated flavones): 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) 及5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF) 在預防、改善粥狀動脈硬化 (atherosclerosis) 上的功效及其分子機轉。實驗設計主要探討此兩種多甲氧基類黃酮對於 (1) THP-1單核球分化成巨噬細胞 (monocyte-to- macrophage)、(2)巨噬細胞轉變成脂泡細胞 (foam cell formation) 、(3)人類肝細胞 (HepG2) 脂質代謝等三方面的影響。
研究結果顯示HMF可有效降低PMA (phorbol-12-myristate-13-acetate, 30 nM) 所誘導分化THP-1單核球對DiI標示 (labelled) 的氧化型LDL (oxLDL)及乙醯化LDL (acLDL) 的吞噬，但是5-OH-HxMF卻無抑制功能。HMF 及5-OH-HxMF對PMA所誘導的CD36表面蛋白及mRNA表現皆無顯著影響; 僅20 M HMF對SR-A 的mRNA 表現有顯著抑制。
接著探討此兩種多甲氧基類黃酮對THP-1所衍生的巨噬細胞轉變為脂泡細胞之抑制功效。RT-Q-PCR的實驗結果顯示，HMF及5-OH-HxMF皆能顯著的減少了清道夫受體CD36的mRNA表現，並降低巨噬細胞吞噬oxLDL的能力。
本研究最後一部份探討此兩種多甲氧基類黃酮對於肝細胞株HepG2吞噬LDL的能力的影響，流式細胞儀的結果呈現5-OH-HxMF較HMF能更有效促進吞噬LDL的能力及LDLR mRNA之表現。HMF與5-OH-HxMF皆能抑顯著的減少肝細胞三酸甘油脂生合成之關鍵酵素DGAT2 的mRNA的表現。
綜合以上結果，HMF相較於5-OH-HxMF能有效抑制THP-1單核球分化成巨噬細胞階段吞噬修飾型LDL的能力 ; 也能抑制單核球衍生的巨噬細胞的清道夫受體的基因表現，進而減低修飾型LDL的吞噬，因此可能具有防止脂泡細胞生成的功效。但是5-OH-HxMF較能促進HepG2吞噬LDL的能力及LDLR 的表現；此外HMF與5-OH-HxMF皆能抑制三酸甘油脂生合成之關鍵酵素DGAT2的表現。
Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease. To clarify the possible role of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) and 5-hydroxy-3,6,7,8,3',4'- hexamethoxyflavone (5-OH-HxMF), on the prevention of atherosclerosis, we investigated their effects on THP-1 monocyte-to-macrophage differentiation, foam cell formation of THP-1-derived macrophages and lipid homeostasis in HepG2 liver cells.
The uptake of DiI labeled oxidatively modified LDL (oxLDL) and acetylated LDL (acLDL) was strongly increased in PMA-stimulated THP-1 monocytes as evidenced by flow cytometry analysis. The treatement of HMF attenuated PMA-indiced DiI-modified LDL uptake indicated the functions of scavenger receptors being blocked. However, neither CD36 surface protein nor mRNA expression was altered with the treatement of HMF or 5-OH-HxMF as compared with PMA alone.
Both HMF and 5-OH-HxMF equally inhibited the formation of foam cells as evidence by the less expression of CD36 mRNA as well as pronouncedly reduced uptake of modified LDL in THP-1 derived macrophages.
In human hepatoma cell line HepG2, 5-OH-HxMF significantly induced LDLR activity and transcription. Both HMF and 5-OH-HxMF decreased the mRNA expression of DGAT2, the key enzyme involved in the hepatic triacylglycerol biosyntheses.
Current results suggest that HMF and 5-OH-HxMF have diverse anti-atherogenic bioactivities. HMF is more potent in inhibiting monocyte-to-macrophage differentiation than its hydroxylated couterpart, 5-OH-HxMF. HMF and 5-OH-HxMF exhibit similar potency in inhibiting foam cell formation. 5-OH-HxMF exhibits stronger hypolipidemic activity than HMF as it can enhance LDLR gene expression and activity and decreased DGAT2 expression. |
| Relation: | 校內一年後公開，校外永不公開，學年度：99，80頁 |
| Appears in Collections: | [Dept. of Biotechnology (including master's program)] Dissertations and Theses
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