鞣花酸對於脂多醣體（LPS）誘導之小鼠巨噬細胞的抗發炎作用研究

The anti-inflammatory action of ellagic acid in LPS-induced macrophage cell line RAW264.7

王秀琦(Shiu-Chi Wang)

指導教授 ： 蒙美津 ； 邱駿紘

亞洲大學/健康學院/生物科技學系碩士班/碩士(2007年)

摘要

發炎現象是身體對付組織損傷、感染或刺激物的方式，其可被非特異性及特異性反應所啟動。而發炎亦為一種可將傷害侷限在局部區域的局部反應，可導致紅、腫、熱、痛。發炎級聯（cascades）的有益作用及發炎對組織的長期性潛在傷害之間存在著微妙的平衡性。假如發炎現象沒有被控制或消退，將會導致諸如慢性氣喘、風濕性關節炎、心血管疾病及特定癌症等疾病的發展。
在多種與發炎相關的病狀中，一氧化氮會顯著地增加。一氧化氮具有包括血管擴張、神經傳導及細胞毒性等多重生物活性。一氧化氮的自由基特性及與過氧化物的高度反應性，使得一氧化氮成為有效的促氧化物質，因而可誘發氧化傷害對多種胞內標的物的潛在性害處。由於一氧化氮的生成控制對人類健康很重要，很多研究團隊因而聚焦在探討一氧化氮由保護轉為有害作用上的機制。
鞣花酸是一種天然存在的植物多酚類，文獻報導顯示鞣花酸對多種致癌物有抗癌及抗致突變的特性。此外，在體外或體內實驗中，鞣花酸都有抗氧化的功效。為了延伸目前對鞣花酸的瞭解，本研究探討鞣花酸對小鼠巨噬細胞株RAW264.7 經脂多醣誘發後之一氧化氮、腫瘤壞死因子-α（TNF-α）及介白素-6（IL-6）的生成，並闡述可能的相關機轉。
研究結果顯示，隨著鞣花酸劑量的增加，能明顯降低因脂多醣（LPS）誘發的一氧化氮產生量。而且， TNF-α 和 IL-6 的產生量也被鞣花酸所抑制。與脂多醣單獨處理比較，鞣花酸的存在可使誘導型一氧化氮合成酶（iNOS）的蛋白質及 mRNA 表現均明顯下降。鞣花酸的添加也會增加IκB 及NF-κB 的表現量。綜合以上結果可知，鞣花酸或許可應用在巨噬細胞調控之發炎性疾病的控制上。

關鍵字

鞣花酸 ； 發炎反應 ； 誘導型一氧化氮合成酶

並列摘要

Inflammation is the body’s way of dealing with tissue damage, infection or irritants and can be initiated by non-specific and specific immune reaction. Inflammation is a local response which limits damage caused by injury to a local site and results in redness, swelling, heat and pain. There is a fine balance between the beneficial effects of inflammation cascades and their potential for long-term tissue destruction. If they are not controlled or resolved, inflammation cascades can lead to the development of diseases such as chronic asthma, rheumatoid arthritis, cardiovascular disease and certain types of cancer.
During many inflammation-associated pathologies, nitric oxide (NO) production increases significantly. NO has a variety of biological activities including vasodilation, neurotransmission and cytotoxicity. The free radical nature of NO and the high reactivity with superoxide renders NO a potent pro-oxidant molecule which is able to induce oxidative damage and potentially harmful toward cellular targets. Owing to the importance of the control of NO production for human health, the attention of many research groups has been focused on the mechanisms responsible of the reversal of NO effects from protective to deleterious.
Ellagic acid (EA) is a naturally occurring plant polyphenol. EA has been shown to possess numerous anticarcinogenic and antimutagenic properties towards a variety of different carcinogens. In addition, EA also has potent antioxidant properties in vivo and in vitro. Expanding upon from current understanding, we examined the effects of EA on lipopolysaccharide (LPS)-induced of nitric oxide (NO), tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）productions using macrophage RAW264.7 cells and revealed the possible mechanisms underlying.
The results indicate that EA inhibited LPS-induced NO production in a dose-dependent manner. Furthermore, EA also decreased the levels of IL-6 and TNF-α. In the presence of EA, inducible nitric oxide synthase（iNOS）protein and mRNA levels were declined significantly as compared with LPS induction alone. Both IκB and NF-κB expressions were also increased with the supplementation of EA. These findings implicate that EA can be applied in the regulation of macrophage-mediated inflammatory diseases.

並列關鍵字

Ellagic acid ； Inflammation ； iNOS

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