植物動情素影響細胞生長及釋放發炎媒介物質之作用機制研究(1/2)

Abstract

植物動情素(phytoestrogens)是一種天然來源的植物化學物。一般來說其 可分類為isoflavones、 coumestans及 lignans等類。它們之所以被稱為植物 動情素是因其化學結構類似於內生性動情素(endogenous estrogens)，且也 會結合到動情素受體-及對於動情素受體-有較高的親和力)，因而 具有表現動情素樣活性(estrogen-like activity)之能力。相較於其它系統， 植物動情素對於免疫系統方面的研究是比較少的。本研究計畫即計畫 以巨噬細胞及腎絲球環間膜細胞實驗模式來探討植物動情素影響細 胞生長及對於發炎媒介物質的合成及釋放作用，以及可能之分子機 制，並且研究動情素受體在其中的角色，進而評估其對於免疫系統可 能具有的病理生理學意義。本年度我們的試驗結果發現植物動情素 -sitosterol、 resveratrol 及genistein在低劑量範圍會促進巨噬細胞及腎絲 球環間膜細胞增生。-sitosterol、 resveratrol 及genistein 亦具有促進巨噬 細胞及腎絲球環間膜細胞對於COX-2蛋白及mRNA表現的能力，且可觀 察到前列腺素PGE2釋放增加；但並不會影響COX-1蛋白表現。而這些 植物動情素的作用會受到動情素拮抗劑ICI182780的部份拮抗。因此， 植物動情素對於免疫系統可能具有某種程度的影響。

Phytoestrogens are naturally occurring plant compounds that are present primarily in soybeans as isoflavones and in flaxseed as lignans. These plant chemicals display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptor beta. Few, if any, studies have been made on the impact of these phytoestrogens on the immune system. The aims of this study, therefore, are twofold. The first goal is to verify the effects of phytoestrogens on the modulation of the cell proliferation and release of inflammatory mediators in macrophages and glomerular mesangial cell. The role of estrogen receptor in these responses is also investigated. Second, we try to investigate the possible molecular mechanism(s) involving in the effect of phytoestrogens on the macrophages and glomerular mesangial cell. In this year’s works, we found that low concentration range (3-100 nM) of phytoestrogens (-sitosterol, resveratrol and genistein) were capable of increasing cell proliferation and inducing the cyclooxygenase-2 protein and mRNA expression in macrophage and glomerular mesangial cell line, which could be partially inhibited by selective estrogen receptor antagonist ICI182780. The expression of COX-1 protein did not affected by these phytoestrogens. These results imply that there are some influences by phytoestrogens in immune system.