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
張德明
國防大學國
目的：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細胞為疾病主軸的類風濕性關節炎有效。本實驗將測試中藥調控類風濕性關節炎發炎與抗發炎 (proinflammatory and anti-inflammatory) 細胞激素基因多形性 (polymorphisms) 在疾病感受性與嚴重度上的意義。
方法：測試類風濕性關節炎致病機轉中主要細胞 (包括滑膜細胞和軟骨細胞) 的變化。基本上本年的實驗內容包括延續去年的結果以中藥雷公藤 測試人類關節滑膜細胞，及人類關節軟骨細胞中細胞激素基因IL-12和IL-12 family genes的變化及細胞增生現象。第二目標則為以建立關節炎老鼠的動物模式，以ELISA和RT-PCR的方法觀察其關節炎老鼠的發病的paw中的細胞激素(IL-1, IL-12, IL-4 and TNF-a)和基底蛋白酶Matrix metalloproteinase(MMP-1 (collagenase)、MMP-3 (strepmelysin) 及TIMP 等酵素)的變化。第三目標則為測試雷公藤靜脈注射類風濕性關節炎的老鼠，分析其中藥對於老鼠的發病的paw中其細胞激素(IL-1、TNF-alpha、IL-4及IL-10) 基底蛋白酶Matrix metalloproteinase(MMP-1 (collagenase)、MMP-3 (strepmelysin) 及TIMP 等酵素)mRNA的產生之變化。第四目標進一步以組織切片和免疫組織染色的方法觀察雷公藤在關節腔中對軟骨細胞和滑膜細胞其MMP-3和TIMP-1之改變狀態從而進一步探討其抗發炎的影響和對疾病嚴重度之改善的程度。
預期結果: 本實驗結果將建立類風濕性關節炎的中藥研究實驗室, 瞭解細胞激素基因在類風濕性關節炎罹病過程的相關性，中藥作用的機轉，並獲得疾病感受性及藥物反應性的指標。
關鍵字：中藥、類風濕性關節炎、細胞激素、基因、雷公藤
Regulation of Cytokine Gene Polymorphisms by Herbal Medicine Affects the Susceptibility and Severity of Rheumatoid Arthritis
Deh-Ming Chang
National defence medical center
Objective: Anti-rheumatic herbal medicine including TWHf and tetradrine (TTD) may regulate T cell and/or B cell function. Rheumatoid arthritis (RA) is basically a T cell autoimmune disease with positive rheumatoid factor. Theoretically, these herbal medicines may play roles in controlling RA. The current study will test the effects of these medicines on pro-inflammatory and anti-inflammatory cytokine polymorphisms.
Methods: Chondrocytes and fibroblasts, major cell types in joint cavity, will be used in this study. Primary cell culture will be incubated with TWHf to test the effects of herbal medicine to cytokine gene expression. Different concentrations of TWHf will be added into the IL-1 stimulated cells to test their effects on the production of IL-12 and IL-12 family genes. Furthermore, we will establish the rat with adjuvant-induced arthritis (AIA), a model relevant to human RA, and use RT-PCR to check the regulation of cytokines(IL-1, IL-4, IL-10, and TNF-alpha) expression durin
關鍵字：Cytokines,Arthritis Rheumatoid,chondrocyte,Chinese herbs
