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研究生:楊東冀
研究生(外文):Yang, Dong Ji
論文名稱:雙酚類化合物對細菌性脂多醣刺激微小膠質細胞活化之影響
論文名稱(外文):The effects of biphenol compounds on lipopolysaccharide-stimulated microglial cell activation
指導教授:詹銘煥
指導教授(外文):Chan, Ming Huan
學位類別:碩士
校院名稱:國立政治大學
系所名稱:神經科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
畢業學年度:101
語文別:中文
論文頁數:80
中文關鍵詞:和厚朴酚微小膠質細胞抗氧化抗發炎ST-24
外文關鍵詞:HonokiolMicroglial cellsAnti-oxidantionAnti-inflammationST-24
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微小膠質細胞在神經退化性疾病中所扮演的角色與機制,在目前許多研究中發現與氧化壓力和發炎反應有關。和厚朴酚 (honokiol)
[2-(4-hydroxy-3-prop-2-enylphenyl)-4-prop-2-enylphenol] 又稱異厚朴酚,為木蘭科植物厚朴 (Magnolia officinalis) 的主要活性成份之一,結構為具有雙丙烯基的多酚化合物 (C18H18O2,MW=266.33),且具有抗氧化和抗發炎的作用。ST-24 化合物為和厚朴酚的衍生物,用和厚朴酚分子結構為主體修飾而成的化合物,本研究針對和厚朴酚與 ST-24 化合物在細菌性脂多醣刺激微小膠質細胞活化反應中的抗氧化與抗發炎能力作探討。實驗以 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) 分析細胞粒線體的還原能力,藉此判斷細胞的存活率。吉爾任試劑 (Griess reagent) 用來測量藥物對活化後的微小膠質細胞產生活性氮自由基 (reactive nitrogen species, RNS) Nitric oxide (NO‧) 的影響。MTT 與吉爾任試劑分析結果顯示,和厚朴酚與 ST-24 在低濃度不會造成細胞死亡且具有減緩細菌性脂多醣刺激微小膠質細胞過度活化所產生的活性氮自由基。本論文的目標除了比較和厚朴酚與 ST-24 化合物的抗氧化及抗發炎能力外,也探討減緩微小膠質過度活化可能的分子機制。透過觀察細胞型態和西方墨點法,發現給予和厚朴酚與 ST-24 藥物可以減少微小膠質細胞因為 LPS 刺激所產生的偽足、iNOS 及 COX-2 蛋白質表現。而給予和厚朴酚與 ST-24 藥物,則會回復 iNOS 上游分子 PI3K/Akt 蛋白質表現。實驗結果顯示和厚朴酚與 ST-24 可能透過 PI3k/Akt 這個分子機制去調控微小膠質細胞過度活化,但仍需進一步的實驗確認。

The role and mechanisms of microglia cell in neurodegenerative diseases might be related to oxidative stress and inflammatory responses. Honokiol is one of the main constituents from Magnolia officinalis. The structure of honokiol possesses a biphenolic structure with two allyl groups (C18H18O2, MW=266.33) that has anti-oxidative and anti-inflammatory effects. In addition, the anti-oxidative and anti-inflammatory properties of honokiol and ST-24 compounds were explored as well as their inhibitory effect on over-activated microglial cells in this study. In the present study, the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to assess mitochondrial activity, reflecting cell survival. The Griess reagent was used to detect the effects of (reactive nitrogen species, RNS) Nitric oxide (NO‧) in activated microglial cells with honokiol and ST-24.The results show that honokiol and ST-24 did not induce cell death in lower concentrations. Both biphenolic compounds attenuated nitric oxide free radical productions in LPS-stimulated over-activated microglial cells. Besides compared honokiol and ST-24 capability of anti-oxidation and anti-inflammation, this study also explored the biological molecular mechanisms of attenuating over-activated microglial cells. By observation of cell morphology and Western blot, we found that honokiol and ST-24 can reduce pseudopodia, and increases in iNOS and COX-2 protein expression induced by LPS in microglia .Honokiol and ST-24 could restore the upstream molecular PI3K/Akt protein expression. The results suggested that honokiol and ST-24 regulated excessive activation of microglia through PI3K/Akt pathway.
謝誌 I
中文摘要 II
ABSTRACT IV
目錄 VI
表次 VIII
圖次 IX
縮寫對照表 XI
中英文名詞對照表 XII
第一章 緒論及文獻回顧 1
第一節、前言 1
第二節、自由基的簡介及發炎反應 4
第三節、微小膠質細胞的簡介 10
第四節、雙酚類化合物之簡介 14
第五節、實驗目的與假說 17
第二章 實驗材料與實驗方法 18
第一節、實驗材料 18
第二節、實驗方法 20
第三節、實驗數據分析 24
第三章 實驗設計 25
目標(一) 建立內毒素 (脂多醣) 對微小膠質細胞活化之模式 25
目標(二) 評估內毒素 (脂多醣) 與藥物所引起微小膠質細胞過度活化及細胞凋亡 26
目標(三) 評估雙酚類化合物對內毒素引起微小膠質細胞型態改變之影響 27
目標(四) 評估觀察同時給予內毒素 (脂多醣) 和不同藥物後對內毒素 (脂多醣) 所引起微小膠質細胞過度活化之作用 27
目標(五) 確認HONOKIOL及ST-24號化合物是否是透過 PI3K/AKT 路徑改善內毒素 (脂多醣) 所引起微小膠質細胞過度活化之分子機制 28
第四章 實驗結果 29
一、內毒素 (脂多醣) 對微小膠質細胞存活之影響 29
二、雙酚類化合物對內毒素引起微小膠質細胞活化及細胞死亡之影響 32
三、雙酚類化合物對內毒素引起微小膠質細胞型態改變之影響 35
四、雙酚類化合物對內毒素引起微小膠質細胞發炎反應之影響 45
五、雙酚類化合物抑制內毒素引起微小膠質細胞活化反應之分子機制 48
第五章 討論 51
第六章 結論 56
第七章 參考文獻 57
1.期刊論文 57
2.書籍論文 67
3.網路資源 67
附錄 68

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2.書籍論文
顏正華, “中藥學(上)”, 知音出版社, 民國八十三年二月初版二刷, 320頁。
莊朝欽。(2009)。和厚朴酚抑制巨噬細胞中細菌內毒素所誘發之細胞激素表現。國立台灣海洋大學食品科學系碩士論文。
卓俊宏。(2010)。芳香烴受體在微小膠細胞活化過程中所扮演的角色。台北醫學大學 醫學院 醫學科學研究所碩士論文。
楊雅婷。(2005)。細胞自然凋亡與發炎反應參與在脂多醣刺激腦微膠細胞移動及聚集現象。國立陽明大學解剖暨細胞生物學研究所碩士論文。
3.網路資源
中藥知識學習網

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