- 學位論文
維生素C保護骨關節軟骨作用機制研究
Study on the Mechanism of Ascorbic Acid in Protecting Articular Cartilage
摘要
退化性關節炎是最常見的關節退化性疾病，主要發生於關節軟骨，而造成疼痛與不良於行，故延緩關節受損成為當今預防醫學重要的課題。先前文獻指出關節軟骨基質流失是造成退化性關節炎的主要因子，而營養元素Ascorbic acid (Vit. C)與軟骨基質形成有密切相關，具有延緩退化性關節炎的潛力。本論文以碘醋酸鈉(MIA)誘發人類軟骨肉瘤細胞株(SW1353)傷害與誘導Wistar大鼠膝部退化性關節炎之體內試驗模式，探討Ascorbic acid保護機制。體外實驗結果顯示5 μM以上MIA濃度可以抑制SW1353細胞生長、增加氧化壓力、促進細胞凋亡及增加醣蛋白基質流失。此外利用即時定量PCR技術分析發炎細胞激素IL-6、IL-17A和TNF-α及基質金屬蛋白酶MMP-1、MMP-3和MMP-13的mRNA表現皆有顯著增加，而這些促使SW1353細胞傷害的作用可以藉由投予100 μM Ascorbic acid來抑制。再進一步以MIA注射於Wistar大鼠膝部誘發類似退化性關節炎的病理變化作為動物模式，利用管餵方式讓老鼠攝入不同劑量Ascorbic acid溶液，實驗結果重要發現Ascorbic acid的效用不隨劑量增加而增強，而以100 mg/kg食用劑量比200或300 mg/kg劑量更能有效降低退化性關節炎病變。 綜合上述結果得知，Ascorbic acid除了抗氧化功效之外，並具有保護關節軟骨功效，提供骨關節保健學理依據，及生技產業應用價值。
並列摘要
Osteoarthritis (OA) is the most prevalent joint disease. Dietary intake of ascorbic acid relates to a reduction in cartilage loss and OA. This study examined the efficacy of ascorbic acid (vitamin C, Vit. C) to prevent OA with the in vitro chondrosarcoma cell line (SW1353) and the in vivo monosodium iodoacetate (MIA)-induced OA rat. Results demonstrated that, in SW1353 cells, treatment with 5 μM MIA inhibited cell growth and increased oxidative stress, apoptosis, and proteoglycan loss. In addition, the expression of the pro-inflammatory cytokines of IL-6, IL-17A, and TNF-α as well as matrix metalloproteinases (MMPs) of MMP-1, MMP-3, and MMP-13 were increased. All of these MIA-induced changes could be prevented with the treatment of 100 μM ascorbic acid. In an animal model, intra-articular injection of MIA-induced cartilage degradation resembled the pathological changes of OA, treatment of ascorbic acid could lessen these changes. Unexpectedly, ascorbic acid’s effects did not strengthen with the increasing dosage, while the 100 mg/kg dosage was more efficient than the 200 or 300 mg/kg dosages. Ascorbic acid possessed multiple capacities for prevention of OA progress, including a decrease in apoptosis and in the expression of pro-inflammatory cytokines and MMPs in addition to the well-known antioxidation. Accordingly, we find that ascorbic acid has effects on articular cartilage in addition to its well-known anti-oxidation and has potential to be a preventive agent for joint health care. Our approaches would provide foundation for ascorbic acid application in biotechnological industry.