探討低氧誘導因子以及葡萄糖轉移子對於葡萄糖胺治療退化性關節炎中的分子機制(一)

Study HIF-1α and GLUT-1 molecular mechanisms of glucosamine HCl on osteoarthritis (一)

林育如(Yu-Ju Lin)

指導教授 ： 陳建和

共同指導教授 ： 許明照

臺北醫學大學/醫學院/醫學檢驗生物技術學研究所/碩士(2007年)

https://doi.org/10.6831/TMU.2007.00077

摘要

依據臨床發現，退化性關節炎病人口服葡萄糖胺 (glucosamine HCl) 最後到達血液濃度並不如in vitro實驗研究的有效濃度，卻仍對病人的疼痛及關節修復有一定的效果，因此本實驗使用葡萄糖胺glucosamine HCl來觀察其對於IL-1β誘發chondrosarcoma SW1353細胞間質水解酵素 (Matrix Metallo- proteinase)的影響，發現高劑量的glucosamine HCl可以抑制低濃度IL-1β所引起的MMPs的mRNA及蛋白質表現，也可以抑制IL-8的mRNA表現，並且使用低劑量的glucosamine HCl則可以抑制高濃度IL-1β引起的發炎反應，實驗結果與臨床應用glucosmaine HCl治療關節炎的現象相符。另外，為了更接近關節環境，本實驗另進行正常氧氣濃度與低氧環境的對照，我們發現除了低氧環境會誘導低氧誘導因子 (HIF-1α) 蛋白表現之外，在低氧環境下單純使用IL-1β誘導的MMPs蛋白表現會降低，而且glucosamine HCl抑制MMPs的效果也會更明顯，同時我們也發現軟骨細胞受到IL-1β及低氧環境的誘導，葡萄糖轉移子 (GLUT-1) 表現量上升，依上述結果推論，HIF-1α及GLUT-1可能是glucosamine治療退化性關節炎的重要機制。

關鍵字

退化性關節炎 ； 細胞激素 ； 細胞間質水解酵素 ； 軟骨瘤細胞 ； 葡萄糖胺 ； 低氧誘導因子 ； 葡萄糖轉移子

並列摘要

Clinical studies have shown that after oral administration of a therapeutic dose of glucosamine HCl, a low blood concentration of glucosamine can be achieved, but it does work to diminish pain and repair the cartilage for osteoarthritic patients. Although in vitro data cannot be extrapolated to pathophysiological conditions in humans, our data suggest the effects of action by which glucosamine HCl could modulate IL-1β induced MMPs expression by chondrosarcoma SW1353 cells. The data shows high concentration of glucosamine HCl can reduce the mRNA and protein expression of MMPs which induced by low concentration of IL-1β; low concentration of glucosamine HCl can reduced the inflammatory response up-regulated by high concentration of IL-1β. The data is to comform to clinical application. Besides, we compare the different effects under normoxia and hypoxia to draw on the real condition in human cartilage. HIF-1α protein level would be up-regulated under hypoxia, and furthermore, the level of MMPs protein expression that induced by IL-1β was lower under hypoxia condition. The inhibition of MMPs by glucosamine HCl was more in apparent. We also found GLUT-1 protein expression would up-regulated under IL-1β and hypoxia treatment by chondrocytes. To sum up the results, we suggested HIF-1α and GLUT-1 may be the important mechanisms for therapeutic of glucosamine HCl on osteoarthritis.

並列關鍵字

osteoarthritis ； IL-1β ； matrix metalloproteinases ； chondrosarcoma cell ； glucosamine HCl ； hypoxia-induced factor-1α ； glucose transporter-1

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