https://scholars.lib.ntu.edu.tw/handle/123456789/83012
標題: | 透明質酸與施德丁於脂多醣體誘發猪軟骨細胞發炎及細胞凋亡反應之作用研究 Effects of Hyaluronic Acid and Statins against LPS-induced Inflammation and Apoptosis in Porcine Articular Chondrocytes |
作者: | 羅朝棟 Loo, Siow-Tung |
關鍵字: | 玻尿酸;施德丁;退化性關節炎;軟骨細胞;脂多醣體;發炎反應;Hyaluronic acid (HA);Statin;Osteoarthritis;Chondrocytes;Lipopolysaccharide;Inflammation | 公開日期: | 2009 | 摘要: | 關節內注射玻尿酸是目前臨床上針對退化性關節炎常用的一種治療。降血脂藥物施德丁近年來被發現具有多效作用,例如:抗發炎反應與減低基質降解酶之表現。本論文的目的為探討玻尿酸與施德丁於體外退化性關節炎模式之治療作用。我們將 0.1mg/ml 的玻尿酸(臨床等級:雅節)混合不同濃度(5μM, 10μM, and 50μM)的新伐他丁(脂溶性)或普伐他丁(水溶性),然後作用於受脂多醣體(內毒素)誘導發炎及細胞凋亡反應的猪軟骨細胞。我們所進行的檢測分析包含有:施德丁之細胞毒性、細胞增殖、NF-κB 轉錄因子活性、一氧化氮釋放量、DNA 片斷化以及IL-1β、TNF-α、IL-6、iNOS、Caspase 3、MMP-1、MMP-13、COL2A1 的基因表現量。我們發現雖然玻尿酸混合50μM 之新伐他丁(H50S)可以有效降低IL-1β、 IL-6、iNOS、caspase 3、MMP-1、MMP-13 的基因表現。但它卻具有細胞毒性以及有抑制細胞增殖的作用。綜合所有結果,我們認為玻尿酸混合50μM 之普伐他丁(H50P)為最具有治療效果的組合。經結果分析得知它能有效的抑制NF-κB 轉錄因子的活性、降低一氧化氮的產生量、降低IL-1β、TNF-α、IL-6、iNOS、caspase 3、MMP-1、MMP-13 的基因表現量。因此,我們認為玻尿酸混合施德丁作為關節內注射劑有可能可以應用於減輕退化性關節炎之症狀。 Intra-articular therapy with hyaluronic acid (HA) is commonly used in osteoarthritis treatment. Lipid-lowering drug statins have been shown to have pleiotropic effects such as anti-inflammatory and reduces matrix-degrading enzymes expression. The objective of this study is to examine the therapeutic effects of statin and hyaluronic acid within an in vitro osteoarthritis model. 0.1mg/ml of HA (ARTZ Dispo®) in combination with different doses (5μM, 10μM, and 50μM) of simvastatin (lipophilic) or pravastatinhydrophilic) were treated to LPS-induced inflammation and apoptosis in porcine articular chondrocyes. We evaluated cytotoxicity, cell proliferation, NF-κB activity, NOroduction, DNA fragmentation, and gene expression of IL-1β, TNF-α, IL-6, iNOS, caspase 3, MMP-1, MMP-13, and COL2A1. Although results showed that the expressionf IL-1β, IL-6, iNOS, caspase 3, MMP-1, and MMP-13 were found significantly decreased when treated with HA in combination with 50μM simvastatin (H50S). However, simvastatin shown to have cytotoxicity effect and inhibits cell proliferation. Base on our findings, HA in combination with 50μM of pravastatin (H50P) appear to have the greatest therapeutics effects. It had shown to have suppress NF-κB activity,reduce NO production, and attenuate IL-1β, TNF-α, IL-6, iNOS, caspase 3, MMP-1, andMP-13mRNA expression. Therefore, we suggest that intra articular injection of HA in combination with statin may be feasible for relieve symptoms of knee osteoarthritis. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/183726 |
顯示於: | 醫學工程學研究所 |
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ntu-98-R96548051-1.pdf | 23.53 kB | Adobe PDF | 檢視/開啟 |
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