探讨山苦瓜三萜类分子的抗发炎效果及分子机制.doc

探討山苦瓜三萜類分子的抗發炎效果及機制Characterization of the anti-inflammatory effect and molecular mechanism of a triterpene isolated from wild bitter melon 研究生：郭靖怡 Kuo, Ching-Yi 指導教授：鄭雪玲 Cheng, Hsueh-Ling 【摘要】 胰島素抗性為引起第二型糖尿病的主要原因。研究發現肥胖者容易產生胰島素抗性，原因是肥胖者的脂肪組織會分泌較大量的發炎性細胞激素，如TNF- tumor necrosis factor- 、IL-1 interleukin-1 、IL-6 interleukin-6 等，而造成了慢性的發炎反應，此長期持續發炎反應會導致胰島素抗性的發生。本實驗室於前期研究中，由山苦瓜 Momordica charantia 花蓮二號篩選出一三萜類化合物RA2-19，發現RA2-19能改善由TNF- 所引起的胰島素抗性並促進細胞對葡萄糖的吸收。同時，也發現RA2-19可緩解TNF- 所造成的發炎反應。因此，本研究的目的是進一步分析RA2-19的抗發炎效果及其分子機制。結果顯示RA2-19能夠減少TNF- 及IL-1 所引起的發炎性因子的表達，包括iNOS、TNF- 、IL-1 及IL-6。進一步探討其機制發現RA2-19可以抑制發炎反應路徑中的IKK I B kinase 的活化與I B inhibitor of NF-κB 的磷酸化，抑制NF- B進入到細胞核中，所以降低發炎反應的產生。山苦瓜、胰島素抗性、發炎反應、三萜類化合物、TNF- 、IL-1 Insulin resistance is a major causative factor for the development of type II diabetes mellitus. Lines of evidence suggested that the adipose tissues of obese individuals secrete a higher amount of inflammatory cytokines such as TNF- , IL-1 and IL-6, which induce chronic, low-grade inflammatory reactions that result in insulin resistance. Previously, a triterpene, RA2-19, was isolated from wild bitter melon Momordica charantia strain WB24. RA2-19 was shown to ameliorate insulin resistance induced by TNF- and promote glucose uptake of cells. Meanwhile, RA2-19 was able to reduce inflammatory reactions induced by TNF- . Therefore, the objective of this study is to further analyze the anti-inflammatory activity of RA2-19 and the underlying mechanism. The data revealed that RA2-19 is able to reduce the expression of inflammatory factors induced by TNF- or IL-1 , including iNOS, TNF- , IL-1 and IL-6. Exploration of the underlying mechanism manifested that RA2-19 could inhibit the activation of IKK I B kinase and the phosphorylation of I B inhibitor of NF-κB , resulting in hindered entry of NF B into the nucleus. This explains the effect of RA2-19 on the inhibition of inflammatory reactions induced by TNF- . Keywords：wild bitter melon; insulin r