引朵美辛與葡萄糖胺調控人類軟骨瘤細胞Aggrecan 和MMP-3表現之研究

Indomethacin and Glucosamine Hcl modulated the expression of aggrecan and matrix metalloproteinase-3 by human chondrosarcoma cell

陳喜玲(Hsi-Lin Chen)

指導教授 ： 陳建和 ； 梁有志

臺北醫學大學/醫學院/醫學檢驗生物技術學研究所/碩士(2006年)

摘要

退化性骨關節炎Osteoarthritis ( OA ) 在目前人口逐漸高齡化的社會中發生率愈來愈高 , 而引朵美辛 ( Indomethacin ) 是一種非類固醇類的止痛抗發炎藥物 ( Non -steroidal anti-inflammatory drugs , NSAIDs ); 葡萄糖胺( Glucosamine ) 是構成關節軟骨glycosaminoglycans( GAG ) 雙醣類的基本結構。研究發現, 退化性 骨關節炎病人的間質分解酵素 ( MMP-3 ) 表現明顯 , 本篇論文主要探討不同劑量的Indomethacin、Glucosamine Hcl對經IL-1β 誘導的軟骨細胞的MMP-3及Aggrecan 的mRNA及蛋白質量表現。我們的實驗發現, 細胞中的MMP-3表現量隨著Indomethacin 劑量的增加而逐漸被抑制,PGE2的分析結果也是同樣被抑制;另外,在Glucosamine部份,隨著劑量的增加, 其MMP-3 表現量會被抑制, 而時間點的增加,Aggrecan的表現量也有增多的趨勢,依我們結果證明Indomethacin 和 Glucosamine Hcl 確實可有效抑制軟骨細胞所產生的MMP-3,PGE2及刺激Aggrecan的產生。總之,依我們結論提供一個有力的證明,對退化性骨關節炎是有幫助的。

關鍵字

骨關節炎,引朵美辛,葡萄糖胺,間質分解酵素,醣蛋白聚合物,軟骨瘤細胞,介白質-1,

並列摘要

The incidence of Osteoarthritis ( OA ) is more higher in progressive elder population now. Indomethacin ,an non-steroid anti-inflammatory drugs ( NSAIDs ) , Glucosamine Hcl is a basic structure of glycosaminoglycan ( GAG ). OA patients obviously have expressed MMP-3 . In this study,we examined the effects of the Indomethacin and Glucosamine Hcl on the mRNA and protein levels of the proteoglycan aggrecan on the activity of matrix metalloproteinase ( MMP-3 ) in cultured human IL-1β induced chondrocyte. The results indicated MMP-3 activity gradually inhibited as the more dose of indomethacin, the same as PGE2 assay. Besides , MMP-3 mRNA will be inhibited as the dose of Glucosamine Hcl and time accumulate , and aggrecan also have this increased trend. Our datas strongly prove Indomethacin and Glucosamine Hcl can inhibit MMP-3 , PGE2 and stimulate aggrecan. These results provide a cogent mechanism to support beneficial effect with Osteoarthritis .

並列關鍵字

Indomethacin , matrix metalloproteinases , Glucosamine Hcl , Aggrecan , chondrosarcoma , IL-1β, Osteoarthritis

參考文獻

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