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題 名 | 中藥調控細胞激素基因在類風濕性關節炎疾病感受性與嚴重度之影響(2)=Regulation of Cytokine Gene Polymorphisms by Herbal Medicine Affects the Susceptibility and Severity of Rheumatoid Arthritis (2) |
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作 者 | 張德明; | 書刊名 | 中醫藥年報 |
卷 期 | 24:2 民95.10 |
頁 次 | 頁49-74 |
專 輯 | 中醫藥基因體及免疫學研究 |
分類號 | 413.41 |
關鍵詞 | 雷公藤; 類風濕性關節炎; 細胞激素; TWHf; Cytokine; Arthritis rheumatoid; |
語 文 | 中文(Chinese) |
中文摘要 | 抗風濕中藥包括雷公藤已知具有T細胞免疫調節之功能,雷公藤更可抑制B細胞產生抗體。因此應對可產生類風濕因子,並以T細包為病主軸的類風濕性關節炎有效。本實驗測試了雷公藤對於類風濕性關節炎致病機轉中主要細胞(滑膜細胞和軟骨細胞)之影響,且以在類風濕性關節炎的發炎機制中重要細胞激素IL-1用來刺激此二細胞,發現在經由低濃度的雷公藤處理的細胞即能明顯抑制由IL-1刺激下所產生MMP-3蛋白質,且雷公藤對於tissue inhibitors of metalloproteinases-1(TIMP-1)的產生並不影響;而在類風濕性關節炎之中。MMP-3蛋白質在關節的破壞中扮演了重要的角色,且在關節腔中MMP-3和TIMP-1之不平衡亦會造成軟骨組織的破壞,所以雷公藤能抑制MMP-3產量且改善MMP-3/TIMP-1之比值,所以在疾病的治療和軟骨的保護上有極大的幫助。因為細胞激素在類風濕性關節炎的致病機轉中扮演重要的角色,在目前的研究指出細胞激素基因之基因表現量(gene expression)極有可能與關節炎的嚴重度有密切的關係,因此我們進一步的分析了是否中藥能改變細胞激素基因的表現量,但經過雷公藤處理16小時的滑膜細胞和軟骨細胞,而其細胞中之細胞激素基因(IL-1ß和IL-12 p35)和趨化素(IL-8)表現量改變-以RT-PCR的方式分析發現,雷公藤能降低在細胞中經由IL-1a所誘發的細胞激素基因(IL-1ß)和趨化激素(IL-8)的表現量,這些在關節炎中具有嚴重的破壞力的細胞激素,但是對於細胞激素IL-12 p35並不影響,而IL-12是在最近的研究中指出,其在類風濕性關節炎的角色並非是一促發炎的因子且對於關節炎的病程有保護之效果。這些證據能夠幫助我們了解到雷公藤在類風濕性關節炎治療上的意義,且能使我們在接下來的實驗研究上順利的進行,即可將其運用於未來中藥治療類風濕性關節炎之參考依據。 |
英文摘要 | Objectives: To test the effects of Tripterygium Wilfordii Hook-f (TWHf) on the regulation of cytokine genes of synovial cells and chondrocytes and to identify their potential mechanisms of action in the therapy for rheumatoid arthitis (RA). Methods: Synovial fibroblasts and chondrocytes have been used as the target cells on account of their predominant roles in RA. At first, we tested the effects of TWHf on IL-1 mediated MMP-3 and TIMP-1 production. Human chondrocyte and RA patient's synovial fibroblasts were incubated with 1ng/ml IL-1 and different concentrations of TWHf for 16 hours. Secondly, we tested the effects of TWHf on cytokine genes (IL-1ß and IL-12 P35) and chemokine gene (IL-8) expression from both fibroblast and chondorcyte cells. Results: We found TWHf could inhibit the IL-1α-induced production of MMP-3 in both synovial and chondrocyte cells, but it did not effect TIMP-1 production. In contract, TWHf could change the ratio of MMP-3:TMP-1 on synovial and chondrocyte cells stimulated with IL-1α. In addition, TWHf also suppressed the IL-1α-induced cytokine gene of IL-1ß and IL-8 mesenger RNA levels in synovial and chondrocyte cells. But the production of IL-12 p35 mRNA was on changed in the IL-1α treated synovial and chondrocyte cells. Furthermore, the gene expression of MMP-13 was also inhibited by TWHf in the IL-1α treated human chondrocyte cells. Couclusion: Our results demonstrated the mechanisms of action of TWHf and inducated their potential role in treating RA. The other effects of TWHf on RA are under investigation. |
本系統中英文摘要資訊取自各篇刊載內容。