臺灣博碩士論文加值系統

全身性紅斑性狼瘡(systemic lupus erythematosus；SLE)為一種機制複雜的自體免疫疾病。主要特徵為B-cell活化及大量的自體抗體產生，伴隨著細胞免疫也跟著活化促進細胞激素分泌。近來有研究指出SLE病患除了免疫紊亂外，在臨床上也出現代謝疾病的徵狀，如血中胰島素濃度升高且血漿中出現抗胰島素抗體(Anti-insulin antibodies; AIA)。本論文研究篩選87 位SLE病患作為實驗受試者，分別利用疾病種類(SLE/aCL+ vs. SLE/aCL-)、疾病活性指標(SLEDAI>3 vs. SLEDAI<3)、胰島素濃度(insulin>11.8 vs. insulin<11.8) 、抗胰島素抗體 (SLE/IAA+ vs. SLE/IAA-)等四種因子為變因去探SLE病患間其血管黏附因子(包括sICAM-1、sVCAM-1)、Th1細胞激素: IL-12、IL-18、INF-γ、TNF-α和Th 2細胞激素：IL-4、 IL-10、IL-6、TGF-β的差異。結果顯示，有aCL抗體的患者TGF-β和INF-γ均顯著高於沒有aCL抗體患者。當病患SLEDAI大於3時，血漿中血管黏附因子(包括sICAM-1、sVCAM-1)和細胞激素(包括IL-18、TNF-α)濃度都較SLEDAI小於3組高。若以所有受試者的胰島素濃度80百分位11.08 μU/ml，將 SLE病患分為兩組，TNF-α和IL-18兩組相較有統計上顯著差異。雙變數相關性統計分析結果發現，同屬血管黏附因子的sICAM-1和sVCAM-1之間呈現正相關。在細胞激素方面，TNF-α這促發炎細胞激素與其他細胞激素間比較有明顯的相關性。抗發炎激素IL-6和IL-10在本實驗分析結果成正相關，表示體內正試圖抵抗降低紊亂的免疫反應。綜合上述，本研究討論的四種變因對SLE病患其黏附因子與細胞激素的分泌具影響性。當SLE病患分別處於SLE/aCL+、SLEDAI>3、insulin>11.08μU/ml、SLE/IAA+，相較其他SLE病患，對體內分泌Th1細胞激素具有顯著的影響。此外，本受試者胰島素濃度偏高，但血糖濃度在適當範圍內，14%病患體內有IAA抗體，且HOMA IR 和HOMA β-cell均有偏高情形，表示患者有胰島素阻抗問題，未來罹患心血管疾病機率提高。

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by ample autoantibody production. During recent decades, some studies suggested that SLE patients not only have deposit of immune complexes but also have metabolic syndrome, such as increased insulin concentration and anti-insulin antibody (AIA). The purpose of this study was to determine the concentrations of adhesion molecules (sICAM-1 and sVCAM-1) and Th1- and Th2-derived cytokines (IL-12, IL-18, INF-γ, TNF-α, IL-4, IL-10, IL-6, TGF-β) in SLE patients under disease-specific and metabolic conditions. Eighty-seven SLE patients were divided into subgroups according to disease status (SLE/aCL+ vs. SLE/aCL-), disease activity (SLEDAI < 3 vs. SLEDAI > 3), fasting insulin concentration (insulin > 11.8 vs. insulin < 11.8), or AIA (SLE/IAA+ vs. SLE/IAA-). Results showed that SLE patients with aCL had higher INF-γ and TGF-β than SLE patients without aCL. When SLE patients’ SLEDAI>3, concentrations of sICAM-1, sVCAM-1, IL-18, and TNF-α were higher than these in SLEDAI<3 subgroup. TNF-α and IL-18 had a significant correlation. TNF-α compared with other cytokines had significant difference in SLE subgroups. IL-6 and IL-10 had a positive significance. In summary, concentrations of adhesion molecules and Th1- and Th2-derived cytokines differed in SLE patients under different clinical manifestations and metabolic conditions. SLE patients with SLE/aCL+, SLEDAI>3, insulin >11.8, or SLE/IAA+ compared with other patients showed different inflammatory patterns based on circulating levels of adhesion molecules and cytokines.

目 錄
書名頁……………………………………………………………………………….....i
論文口試委員審定書…………………………………………………………………ii
授權書……………………………………………………………………………… ..iii
中文摘要……………………………………………………………………………...iv
英文摘要………………………………………………………………………………v
致謝…………………………………………………………………………………...vi
目錄…………………………………………………...……………………………...vii
表目錄………………………………………...…………………………………........xi
圖目錄…………………………………………………………………………….….xii
第一章 前言…………………………………………………………………………1
第二章 文獻回顧……………………………………………………………………3
2. 1自體免疫疾病-全身性紅斑性狼瘡……………………………………..………..3
2. 2 抗磷脂質症候群…………………………………………………………………8
2. 3 疾病活性指數……………………………………………………………………9
2. 4 細胞激素與SLE疾病關係……………………………………………………10
2. 4. 1 SLE與TNF-α濃度相關性………………………………………………15
2. 4. 2 SLE與IFN-γ濃度相關性…………………………………….…………17
2. 4. 3 SLE疾病與TGF-β濃度相關性……………………………………..….19
2. 4. 4 SLE與IL-12濃度相關性……………………………………………..…20
2. 4. 5 SLE與IL-18濃度相關性………………………………………………..22
2. 4. 6 SLE與IL-10濃度相關性……………………………………………….24
2. 4. 7 SLE與IL-4濃度相關性………………………………………………....26
2. 4. 8 SLE與IL-6濃度相關性………………………………………….……..27
2. 5 胰島素與SLE疾病關係………………………………………………..………28
2. 6 黏附因子與SLE疾病關係……………………………………………………..30
第三章 材料與方法………………………………………………………………..32
3. 1 材料……………………………………………………………………………..32
3. 1. 1 藥品………………………………………………………………………..32
3. 1. 2 器材….…………………………………………………………………….32
3. 2 實驗對象與實驗設計…………………………………………………….…….33
3. 3 實驗方法…………………………………………………………………….….34
3. 3. 1 黏附因子： sICAM-1和 sVCAM-1測定……………………………..34
3. 3. 1. 1 sICAM-1 測定…………………………………………...…………34
3. 3. 1. 2 sVCAM-1測定……………………………………………………...35
3. 3. 2 抗胰島素自體抗體 (Insulin autoantibodies；IAA)之測定………………..35
3. 3. 3 細胞激素IL-18、IL-12、IL-6、IL-4、IL-10、INF-γ、TNF-α、TGF-β
測定…………………………………………………………………………..36
3. 3. 3. 1 IL-18測定………………………………………………………..….36
3. 3. 3. 2 TNF-α測定…………………………………………………….……37
3. 3. 3. 3 IFN-γ測定………………………………………………………..…38
3. 3. 3. 4 TGF-β測定……………………………………………………….....38
3. 3. 3. 5 IL-4 測定……………………...………………………………..…..39
3. 3. 3. 6 IL-12測定…………………………………………………………...40
3. 3. 3. 7 IL-6測定………………………………………………….…….…...40
3. 3. 3. 8 IL-10測定………………………………………………….………..41
3. 4 統計方法………………………………………………………………………..41
第四章 結果………………………………………………………………………..43
4. 1 SLE病患的基本資料………………………………………………………….43
4. 2 SLE患者的生化檢測值及相關性分析比較………………………………….44
4. 2. 1 SLE病患生化檢測值之相關性分析…………………………………...44
4. 2. 2 SLE/aCL+ vs. SLE/aCL-…………………………………………………45
4. 2. 2. 1 SLE/aCL+組和SLE/aCL-組之生化檢測值………………………..45
4. 2. 2. 2 SLE/aCL+組和SLE/aCL-組生化檢測值之相關性……………….45
4. 2. 3 SLEDAI ≦3 vs. SLEDAI ＞3………………………………….……..46
4. 2. 3.1 SLEDAI ≦3組和SLEDAI ＞3組之生化檢測值…………………46
4. 2. 3. 2 SLEDAI ≦3組和SLEDAI＞3組的生化檢測值之相關性……….46
4. 2. 4 insulin＞11.08μU/ml vs. insulin≦11.08μU/ml………………………….47
4. 2. 4. 1 insulin＞11.08μU/ml組和insulin≦11.08μU/ml組之生化檢測值..47
4. 2. 4. 2 insulin＞11.08μU/ml和insulin≦11.08μU/ml組的生化檢測值之相
關性………………..………………………………………………..48
4. 2. 5. SLE/IAA+ vs. SLE/IAA-………………………………………………48
4. 2. 5. 1 SLE/IAA+組和SLE/IAA-組之生化檢測值……………………….48
4. 2. 5. 2 SLE/IAA+組和SLE/IAA-組之生化檢測值之相關性…………….49
第五章 討論………………………………………………………………………..61
5. 1 疾病種類對細胞激素及細胞黏附因子的影響………………………………62
5. 2 疾病活性對細胞激素及細胞黏附因子的影響………………………………63
5. 3 胰島素對細胞激素及細胞黏附因子的影響…………………………………67
5. 4 抗胰島素抗體對細胞激素及細胞黏附因子的影響…………………………69
第六章 結論………………………………………………………………………..71
第七章 參考文獻……………………………………………………………………72

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