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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=Regulation of Cytokine Gene Polymorphisms by Herbal Medicine Affects the Susceptibility and Severity of Rheumatoid Arthritis |
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編 次 | 3 |
作者 | 張德明; | 書刊名 | 中醫藥年報 |
卷期 | 25:2 2007.10[民96.10] |
頁次 | 頁281-304 |
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性因子,並以T細胞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--滑膜細胞之影響。 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,因此我們收集類風濕性關節炎置換之關節滑膜,並以在類風濕關節炎的發炎機制中重要細胞激素IL-1用來刺激此細胞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18小時的滑膜細胞,而其細胞中之細胞激素基因(IL-1ß、IL-12 p35和IL-23 p19)和趨化激素(IL-8)表現量改變--以RT-PCR的方式分析,同時以collagen II建立小鼠的關節炎模式,每天給予雷公藤治療,之後進行其小鼠之病理變化和其細胞中之上述細胞激素基因表現量改變。 雷公藤能降低細胞中經由IL-1a所誘發的細胞激素基因IL-23 p19和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,且在小鼠的關節炎模式中,當我們每天給予0.3mg/kg之雷公藤則可在約一個禮拜內消除小鼠後腿腫脹之形況。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。 |
英文摘要 | To test the effects of Tripterygium Wilfordii Hook-f (TWHf) on the regulation of cytokine genes of synovial cells and identify their potential mechanisms of action in the therapy for rheumatoid arthritis (RA). Human synovial fibroblasts from patients of RA were stimulated with or without IL-1α in the presence or absence of THWf. The expression of IL-23 p19 subunit and IL-12 p35 subunits message RNA (mRNA) in human fibroblast like synoviocytes (HFLS-RA) in RA patients were determined by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of IL-23 p19 at the protein level was confirmed by Western blotting. Blockade of NF-kappaB activation was used to verify the mechanism of the induction of p19. Secondly, we tested the effects of TWHf on cytokine genes (IL-1B), chemokine gene (IL-8) and MMP-13 gene expression from fibroblast cells. At last, use animal model of RA determine the function of TWHf in therapy. IL-1α could induce RA fibroblast-like synoviocytes to produce IL-23 P19 subunit. IL-23 p19 mRNA could not be found in unstimulated HFLS-RA. IL-1α induced IL-23 p19 gene expression in HFLS-RA. These responses were observed in both a dose-responsive and time-dependent manner. IL-1α did not obviously enhance gene expression of p35 of IL-12. In addition, the NFkappaB inhibitor pyrrolidine dithiocarbamate (PDTC) down-regulated the expression of IL-23 p19 mRNA induced by IL-α. Furthermore, Chinese herbal TWHf could reduce IL-1α induced-IL-23 p19 expression in HFLS-RA. TWHf has no effect on IL-12 p35 mRNA expression in HFLS-RA. TWHf also suppressed the IL-1α-induced cytokine gene of IL-1ß and IL-8 and MMP-13 messenger RNA levels in synovial. Therapeutic administration of TWHf at 0.3 mg/kg, i.p., every day, significantly reduced the severity of CIA. Our results demonstrated the mechanisms of action of TWHf and indicated their potential role in treating RA. |
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