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博碩士論文 etd-0719110-213155 詳細資訊
Title page for etd-0719110-213155
論文名稱
Title
來自柳珊瑚目的海洋天然物其抗關節炎之作用
Anti-arthritic effects of marine-derived compound obtained from gorgonian coral
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
66
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2010-07-07
繳交日期
Date of Submission
2010-07-19
關鍵字
Keywords
類風濕性關節炎、脂多醣、蝕骨細胞、細胞自溶酵素-K、基質金屬蛋白水解酶-9、滑膜
matrix metalloproteinase 9, synovium, rheumatoid arthritis, lipopolysaccharide, cathepsin K, osteoclast
統計
Statistics
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中文摘要
類風濕性關節炎(rheumatoid arthritis, RA)是一種慢性發炎的疾病,影響許多的組織與器官,尤其是以關節腔的滑膜(synovium)為最嚴重。類風濕性關節炎的症狀主要都是由於細胞發炎(inflammation)所引起,而這類的發炎則會造成細胞浸潤(cellular infiltration)與滑膜增生(synovial hyperplasia),最後導致嚴重的骨質侵蝕(bone erosion)。目前現今在治療類風濕性關節炎的藥物(例如固醇類藥物(steroids)、非固醇類抗發炎藥物(non-steroid anti-inflammatory drugs, NSAIDs)與疾病修飾抗關節炎藥物(disease-modified anti-arthritic drugs, DMARDs))雖能有效地改善其症狀,但也同樣伴隨著許多副作用的產生。因此,開發新的治療類風濕性關節炎藥物是一重要的課題。Excavatolide B (Exc-B)為一種由海洋柳珊瑚所分離出來的海洋天然物。在我們先前的實驗發現,Exc-B會抑制由脂多醣(lipopolysaccharide, LPS)所誘發巨噬細胞(macrophage, RAW 264.7)產生的前驅發炎性物質,誘發型一氧化氮合成酶(inducible nitric oxide synthase, iNOS)與第二型環氧化酶(cyclooxygenase 2, COX-2)的蛋白質表現。而Exc-B對於LPS所引起巨噬細胞產生類似蝕骨細胞(osteoclast-like)活性基因(如細胞自溶酵素-K (cathepsin K)與基質金屬蛋白水解酶-9 (matrix metalloproteinase 9, MMP-9))的表現,也具有顯著抑制的效果。在佐劑誘發關節炎(adjuvant-induced arthritis)的動物模式中,Exc-B不僅可以有效降低外觀型態的腫脹(swelling)與關節炎指數(arthritic index)。同時從組織病理切片上,也發現Exc-B能顯著抑制骨質侵蝕與滑膜增生之現象。因此,以上實驗結果證實,Exc-B能有效抑制類風濕性關節炎的發生。暗示著Exc-B具有發展成為治療類風濕性關節炎之藥物的潛力。
Abstract
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs but principally attacks synovial joints. All the symptoms of RA are mainly caused by cell inflammation, which results in cellular infiltration and synovial hyperplasia, finally leading to severe bone erosion. Existing drugs (steroids, non-steroid antiinflammatory drugs, disease-modifying anti-rheumatic drugs, etc.) can attenuate the symptoms of RA; however, these drugs also have many side effects. Therefore, it is necessary to discover new drugs for RA. Excavatolide B (Exc-B) is derived from the gorgonian coral. In our preliminary observations, Exc-B strongly inhibited lipopolysaccharide (LPS)-induced proinflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW264.7 macrophages. The present study also showed that Exc-B significantly attenuates the expressions of osteoclast-like gene, cathepsin K, and matrix metalloproteinase (MMP)-9 in LPS-treated RAW 264.7 cells. Moreover, in the adjuvant-induced RA animal model, Exc-B effectively reduced the swelling and arthritic index from the morphological viewpoint as well as reduced bone erosion and synovial hyperplasia from the pathological viewpoint. Our data indicates that Exc-B can inhibit disease progression in RA. Hence, Exc-B may serve as a useful therapeutic agent for the treatment of RA.
目次 Table of Contents
目錄...........................................................................1
圖目錄.......................................................................2
中文摘要...................................................................3
Abstract....................................................................4
I. 前言.....................................................................6
II. 實驗材料與方法...............................................15
III. 實驗結果...........................................................24
IV. 實驗討論...........................................................47
V. 附錄...................................................................54
VI. 參考資料...........................................................58

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