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Advanced glycation end products and its soluble receptor in AOSD pathogenic role

By 吳燕晴 and Yen- Ching Wu

Abstract

成人型史迪兒氏症(adult onset Still’s disease,簡稱AOSD) 是一種慢性發炎疾病,患者會有不明原因的發燒、關節炎、皮膚紅疹或其他內臟器官之侵犯,致病機轉目前尚未明瞭。有研究顯示糖化終產物(advanced glycation end products,簡稱AGEs)與慢性發炎有關。在某些慢性發炎疾病,例如全身性紅斑狼瘡(systemic lupus erythematosus,簡稱SLE)等研究中發現AGEs的累積與病程發展有關,但在AOSD患者目前沒有相關的研究。為了探討AGEs及其可溶性RAGE接受器(soluble receptors for advanced glycation end products,簡稱sRAGE) 與AOSD致病機轉的關聯,我們收納52名AOSD患者、36名SLE患者及16名健康者的檢體,以酵素連結免疫吸附法( enzyme- linked immuno- sorbent assay ,簡稱ELISA) 檢測血漿(或血清)AGEs濃度,及可溶性RAGE接受器(能於循環血液中與AGEs接合,阻止AGEs接到細胞膜上RAGE)。由我們檢測的數據發現,活動期AOSD患者檢體的AGEs濃度明顯高於健康對照組( mean± SEM; 19.47± 1.84 &micro;g/ ml比8.45± 0.97μg/ ml; p < 0.001),也明顯高於非活動期AOSD患者( mean± SEM; 7.52± 0.57μg/ ml; p < 0.001)。sRAGE於活動期AOSD患者檢體的濃度明顯低於健康對照組( mean± SEM; 650.7± 59.0 pg/ml比1129.7± 98.7 pg/ ml;p < 0.001),也明顯低於非活動期AOSD患者( mean± SEM; 985.3± 106.9 pg/ ml ; p <0.05),而SLE患者檢體的AGEs 和sRAGE的檢測結果也與AOSD相似。另外AOSD患者檢體的AGEs濃度與疾病活動度的指標activity score (r =0.836 ; p < 0.001)、ferritin ( r =0.372;p <0.05)、ESR(r =0.413;p <0.005)、CRP( r =0.396;p <0.005) 都呈正相關。我們的結果顯示AGEs 和sRAGE可能在AOSD的致病機轉扮演重要角色,且可以做為疾病活動度的監控指標。Adult onset Still’s disease (AOSD) is a chronic inflammatory disease characterized by fever of unknown origin, arthritis, and skin rash. However the etiopathogenesis of AOSD remains unclear. Studies have shown that the levels of advanced glycation end products (AGEs) were associated with chronic inflammation, and were positively correlated with disease duration of systemic lupus erythematosus (SLE). Although AOSD is also an inflammatory disease, there is no any data regarding AGEs in this disease. In order to explore the relationship between AOSD and AGEs as well as their receptors, we enrolled 52 patients with AOSD, 36 patients with SLE, and 16 healthy volunteers, and used the enzyme-linked immunosorbent assay (ELISA) to detect plasma (or serum) levels of AGEs and their soluble receptors for advanced glycation end products (sRAGE). Our results showed plasma (or serum) AGEs levels were significantly higher in patients with active AOSD compared with healthy controls (mean± SEM; 19.47± 1.84 &micro;g/ ml vs. 8.45± 0.97μg/ ml; p < 0.001). Plasma (or serum) AGEs levels were also significantly higher in patients with active AOSD compared with inactive AOSD (mean± SEM; 7.52± 0.57μg/ ml; p < 0.001). Whereas, plasma (or serum) sRAGE levels were significantly lower in patients with active AOSD compared with healthy controls (mean± SEM; 650.7± 59.0 pg/ml vs.1129.7± 98.7 pg/ ml; p< 0.001). Plasma (or serum) sRAGE levels were lower in patients with active AOSD compared with inactive AOSD (mean± SEM; 985.3± 106.9 pg/ ml; p < 0.05). Similarly, plasma (or serum) AGEs levels were higher and sRAGE levels were lower in patients with active SLE compared with inactive SLE or healthy control. Plasma (or serum) AGEs levels were also positively correlated with activity markers of AOSD including a activity score (r =0.836 ; p < 0.001)、ferritin ( r =0.372;p <0.05)、ESR(r =0.413;p <0.005)、CRP( r =0.396;p <0.005).In conclusion our results suggested that AGEs and sRAGE could be useful markers for clinical physician to monitor disease activity of AOSD.中文摘要..................................................i 英文摘要..................................................ii 目錄......................................................iv 圖表目錄..................................................vi 第一章 前言...............................................1 一、糖化終產物及其接受器..................................1 二、成人型史迪兒氏症......................................3 三、全身性紅斑狼瘡........................................5 四、實驗設計..............................................6 第二章 材料與方法.........................................7 一、研究對象..............................................7 二、檢體收集與處理........................................7 三、實驗方法..............................................9 四、統計分析..............................................14 第三章 結果...............................................15 一、AOSD患者、 SLE患者和健康對照組(Healthy control)的性別、年齡分佈與臨床特徵....................................15 二、AOSD患者、 SLE患者和健康對照組血漿(血清)AGEs、sRAGE濃度和PBMC之RAGE mRNA表現量...................................15 三、血漿(血清)AGEs濃度之比較............................15 四、血漿(血清)sRAGE濃度之比較...........................16 五、PBMC之RAGE mRNA的表現量...............................17 六、AOSD患者和SLE患者血漿(血清)AGEs濃度及sRAGE濃度與疾病活動度的關聯性..............................................17 第四章 討論...............................................18 參考文獻..................................................22 圖 表...................................................2

Topics: 成人型史迪兒氏症, 全身性紅斑狼瘡, 糖化終產物, 可溶性糖化終產物接受器, 致病機轉, Adult onset Still’s disease, systemic lupus erythematosus, advanced glycation end products, soluble receptor for advanced glycation end products, pathogenesis
Publisher: 生命科學院碩士在職專班
Year: 2014
OAI identifier: oai:ir.lib.nchu.edu.tw:11455/81159
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