博碩士論文 101224001 詳細資訊




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姓名 謝瑋珊(Wei-shan Hsieh)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 ASIC3或TRPV1基因剔除會減緩單關節炎 誘發的機械性痛覺敏感現象
(Deletion of ASIC3 or TRPV1 gene reduces mono-arthritis-induced mechanical hyperalgesia)
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摘要(中) 自體免疫疾病是一個慢性的情況,起始於自體抗原的免疫功能喪失代表異質的雜亂,而去攻擊特定器官或是多種器官系統。類風溼性關節炎是一種慢性、漸進式、全身性的、特徵是關節滑膜結締組織嚴重破壞的發炎疾病。類風溼性關節炎主要涉及組織的發炎,而不是關節退變。雖然發炎會造成類風濕性關節炎病患的疼痛,但這並不是唯一造成疼痛的原因。 有些病患使用抗發炎疾病修飾抗風濕性藥物治療並不能改善疼痛的情況。關節發炎通常伴隨著組織酸化。因此,酸敏感接受器對於類風溼性關節炎可能扮演關鍵角色。使用兩種基因剃除(ASIC3和TRPV1)的小鼠來研究類風溼性關節炎。每周在關節注射一次5µg CFA,連續四周,用以建立模擬類風溼性關節炎小鼠的動物模式。模擬期間測量關節寬度和關節組織病理變化,以監測關節炎的過程。以Von Frey尼龍絲來評估注射CFA後小鼠的疼痛行為反應。在野生型和基因剔除的小鼠關節注射CFA會誘發二級機械性痛覺敏感現象。ASIC3和TRPV1基因剔除的小鼠可以減緩類風溼性關節炎在後期的機械性痛覺敏感現象。
摘要(英) Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens and represent a heterogeneous group of disorders that afflict specific target organs or multiple organ systems. Rheumatoid arthritis (RA), one of ADs, can be defined as a chronic, progressive, systemic, inflammatory disease of connective tissues characterized by the severe destruction in synovial joints. RA involves primary tissue inflammation rather than joint degeneration. Although inflammation contributes to pain in RA, however, it may not be the only factor. For some patients, pain is not improved despite of the treatment with anti-inflammatory disease-modifying anti-rheumatic drugs. The aim of this thesis is to identify novel genes that are involved in RA-induced pain. Given that joint inflammation is usually accompanied by tissue acidosis, proton-sensing receptors could be the candidates for RA. Two knockout mice (ASIC3-/- & TRPV1-/-) were generated for the RA study. After intra-articular injection into a stifle joint with complete Freund’s adjuvant (CFA) once per week for 4 weeks, long-term mechanical hyperalgesia was developed in wildtype and knockout mice. Both of ASIC3-/- & TRPV1-/- reduced RA-induced mechanical hyperalgesia in the late phase.
關鍵字(中) ★ 關節炎 關鍵字(英) ★ arthritis
論文目次 第一章 緒論 1
1.1自體免疫疾病(Autoimmune diseases) 2
1.1.1系統性紅斑性狼瘡(systemic lupus erythematosus;SLE) 2
1.1.2類風濕性關節炎(rheumatoid arthritis;RA) 3
1.2 類風溼性關節炎的疼痛機制 4
1.2.1 模擬類風溼性關節炎的動物模式 5
1.3 酸敏感的受體和離子通道 6
1.3.1酸敏感離子通道3(ASIC3) 6
1.3.2 辣椒素受體1(TRPV1) 6
1.3.3 TDAG8受體 (T cell death-associated gene 8) 7
1.4臨床用於治療類風濕性關節炎的藥物 8
1.5 研究動機與目的 9
第二章 材料與方法 10
2.1 實驗材料 11
2.1.1 實驗動物 11
2.1.2 實驗藥品 11
2.1.3 紅斑性狼瘡( Systemic lupus erythematosus;SLE)樣品 12
2.2實驗方法 12
2.2.1小鼠基因型的判定 (Genotyping) 12
2.2.2瓊酯膠的置備及電泳分析 12
2.2.3小鼠關節炎模式 13
2.2.4 關節炎程度的評估 13
2.2.5 機械性痛覺行為實驗(Von Frey filament test) 13
2.2.6 蘇木素-伊紅染色 ( hematoxylin and eosin stain、H&E stain ) 14
2.2.7背根神經節的RNA萃取及cDNA合成 14
2.2.8紅斑性狼瘡病患血液中T細胞(CD4)的cDNA合成 15
2.2.9 定量聚合酶鏈反應 (quantitative PCR, Q-PCR) 15
2.2.10血液中cytokine定量分析ELISA( The enzyme-linked immunosorbent assay) 15
2.2.11 統計分析 (Statistics) 16
第三章 結果 17
3.1 在野生型小鼠關節重複注射CFA誘發長期關節疼痛 18
3.2 組織病理學中野生型小鼠在同側腳關節的H&E染色 19
3.3 在慢性關節疼痛中酸敏感受體的基因表現 19
3.4在基因ASIC3 -/-小鼠關節連續注射CFA後,在後期減緩機械性痛覺敏感現象 20
3.5組織病理學中基因ASIC3-/-小鼠在同側腳關節的H&E染色 21
3.6在基因TRPV1-/-小鼠關節連續注射CFA後,在後期減緩關節腫脹和機械性痛覺敏感現象 21
3.7組織病理學中基因TRPV1-/-小鼠在同側腳關節的H&E染色 22
3.8測量TNF-
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指導教授 孫維欣(Wei-hsin Sun) 審核日期 2015-6-22
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