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博碩士論文 etd-0830111-153126 詳細資訊
Title page for etd-0830111-153126
論文名稱
Title
來自台灣軟珊瑚之化合物對於鹿角菜膠誘發老鼠發炎之影響
The effects of compounds obtained from Formosa soft coral on carrageenan-induced inflammation in rats
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
114
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
2011-06-24
繳交日期
Date of Submission
2011-08-30
關鍵字
Keywords
抗發炎、止痛、第二型環氧化酶蛋白質、誘發型一氧化氮合成酶、鹿角菜膠、酯多醣
antinociceptive, anti-inflammatory, lipopolysaccharide, inducible nitric oxide synthase, cycloxygenase-2, carrageenan
統計
Statistics
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中文摘要
近年來,有研究愈來愈認知到許多具有生物活性之天然物,已被從海洋生物中分離出來,然而對於這些以陸地為基礎生物的化學結構非常截然不同。因此,海洋是一個天然藥物的來源。同時在藥物篩選上,具有抗發炎活性物質已經成為一個主要重點,以及在許多研究中證實,發炎反應在許\多人類疾病中所扮演的重要角色。雖然有多種不同的化合物正在進行臨床評估階段,然而與發炎相關疾病上,其研究開發具有抗發炎效果與篩選極具治療性的藥物仍是迫切需要的。本研究針對台灣產柳珊瑚(Briareum excavatum)與台灣產肉質珊瑚(Lobophytum sarcophytoides)針對所含之化合物進行分離、純化及生物活性篩選。在初步離體(in vitro)實驗上發現柳珊瑚(Briareum excavatum)天然化合物Brei與肉質珊瑚(Lobophytum sarcophytoides)之化合物 Sac-1 在酯多醣(lipopolysaccharide, LPS)誘發小鼠巨噬細胞產生發炎反應模式中,具有顯著抑制誘發性一氧化氮合成酶(inducible nitric oxide synthase, iNOS)及第二型環氧化酶蛋白質(cyclooxygenase-2, COX-2)之作用。在活體試驗中,利用皮下注射方式探討天然物Brei化合物在大白鼠腳掌注射鹿角菜膠(carrageenan)所引發發炎疼痛模式下是否具有抗發炎及鎮痛作用。以腳掌容積測量(paw edema)、溫度感異常測試(plantar stimulator analgesia)、機械痛敏測試(allodynia)及負重測試(weight bearing)進行動物行為分析測試,評估大白鼠的發炎與疼痛行為程度。由實驗結果顯示天然物Brei在鹿角菜膠所誘發大白鼠腳掌發炎模式中可減緩腳掌腫脹、熱覺過敏、觸覺疼痛、改善受傷肢負重及有效降低外觀型態的腫脹等現象。在病理組織切片與染色分析結果顯示,Brei 顯著抑制發炎相關性血球細胞的聚集及浸潤,並降低其數量的表現,確實改善組織發炎現象。因此 Brei 可能是一具有抗發炎之海洋天然物,對於急性發炎相關疾病上具有發展潛力之海洋藥物。
Abstract
In recent years, studies have increasingly recognized that many natural products with biological activity have been isolated from marine organisms, while the chemical structures are very different from those of land-based organisms. Therefore, the ocean is a natural drug source. Regarding drug screening, anti-inflammatory activity has become a key point, and many studies confirm that inflammation plays an important role in many human diseases. Many different compounds are now in the clinical evaluation stage. However, the inflammation-related diseases being closely linked, there is an urgent need to study the anti-inflammatory effects as well as screen the therapeutic drugs for research and development. In this study, we isolated and purified compounds from Formosan gorgonian (Briareum excavatum) and Formosan soft coral (Lobophytum sarcophytoides) and investigated biological activities. We confirmed that the natural compound Brei from B. excavatum and the compounds Sac-1 and Sac-2 from L. sarcophytoides produced significant inhibition of the proinflammatory proteins inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-induced murine macrophages (RAW 264.7) cell model. We examined in vivo whether the B. excavatum Brei has anti-inflammatory and antinociceptive effects by using the carrageenan-induced inflammation model. Using the paw-edema assay, we performed several important investigations such as the plantar analgesia test, mechanical hyperalgesia test (allodynia), and weight-bearing analysis of animal behavior to evaluate the degree of pain and inflammation. Our results demonstrate that the natural product Brei can reduce paw-pad swelling, thermal hyperalgesia, threshold latency, and improve the affected limb in the carrageenan-induced inflammatory model. In the histopathology analysis, we showed that Brei significantly inhibited the aggregation and infiltration of inflammation-related blood cells and improved the inflammatory status of the tissues. Therefore, the marine natural compound Brei has anti-inflammatory activity and it can be used as a therapeutic compound for acute inflammation in the near future.
目次 Table of Contents
論文審定書…………………………………………………………………………….i
致謝………………………………………………………………………………….....ii
中文摘要……………………………………………………………............................iii
英文摘要…....................................................................................................................iv
第壹章、前言………………………………………….………………........................1
第貳章、實驗材料與方法…………………………………………………………….9
第參章、實驗結果……………………………………………..……………………..29
第肆章、實驗討論…………………………………………...……...………………..64
第伍章、參考文獻…………………………………………...……...………………..86
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