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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃青真 | |
| dc.contributor.author | Yi-Ning Huang | en |
| dc.contributor.author | 黃懿寧 | zh_TW |
| dc.date.accessioned | 2021-06-13T01:07:55Z | - |
| dc.date.available | 2009-10-13 | |
| dc.date.copyright | 2007-07-27 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-23 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29470 | - |
| dc.description.abstract | 癸酸 (capric acid) 為中鏈脂肪酸 (medium-chain fatty acid)之一，具有抗菌、抗微生物與抗病毒等功效。之前研究指出，癸酸 (capric acid) 可以抑制脂多醣 (LPS) 活化巨噬細胞。本實驗的目的即試圖找出癸酸抑制PGE2產生的機制。癸酸抑制LPS刺激PGE2生成具有劑量效應，其IC50約為8.9 μM；但並不會改變 COX-2蛋白質表現。癸酸於 LPS 刺激後添加，仍可以有效的降低 PGE2 生成。在 LPS刺激之前，先給予癸酸預處理，則不會減少PGE2生成量。
為了驗證基質的獲取是否為限制因子，故在LPS刺激18小時之後，移除培養液再加入外源性的arachidonic acid (AA)，癸酸抑制PGE2 生成的效果依然存在，但抑制程度較低。表示癸酸的抑制效果可能部分來自於降低COX-2酵素活性，另一部份則推測可能源自降低細胞內源性基質獲取。以酵素動力學分析，capric acid對於AA為一種non-competitive inhibition的關係。 以純化酵素為模式，發現 0.5-5 μM 癸酸可降低COX-2之酵素活性達27%；進一步的測試 eroxidase 的活性，癸酸處理亦具有抑制COX-2 活性效應。 本研究結果推論：癸酸降低PGE2生成是經由抑制酵素轉換以及降低酵素的基質獲取。 | zh_TW |
| dc.description.abstract | Capric acid, a member of medium-chain fatty acid, has antibacterial, antimicrobial and antivirus functions. Previous study has indicated that capric acid inhibits PGE2 production in the LPS-stimulated RAW264.7 macrophage cell line. The aim of this study has to examine the mechanism on how capric acid inhibits PGE2 production.
Capric acid inhibited PGE2 production in the LPS imulated RAW264.7 cells in a dose-dependent manner. However, capric acid did not change the COX-2 protein expression as etected by Western Blot Analysis. The inhibition of Capric acid on PGE2 production was also observed when Capric acid and LPS were added simultaneously (p<0.05). Capric acid pretreatment did not result in a reduction in PGE2 production after cells were treated with LPS. To test whether substrate availability could be a limiting factor, medium was supplement with arachidonic acid (AA) after cells were treated with LPS for 18 hours. It was found that the inhibition of PGE2 production could be reduced to a great extent by the supplementation of AA, implying Capric acid might inhibit LPS-stimulated PGE2 production by limiting the substrate availability. However, when capric acid was included in the AA supplemented medium, a slight inhibition of PGE2 production could still be observed (p<0.0001). Kinetic study suggested a non-competitive inhibition before capric acid and AA on PGE2 production in the LPS-stimulated macrophage cells. The effect of capric acid on the activity of purified COX-2 enzyme was also examined. Results showed that Capric acid significantly inhibited COX-2 enzyme activity at a concentration of 0.5, 1 and 5 μM (p<0.05). Capric acid also slightly inhibited the peroxidase activity of the purified COX-2 enzyme. In conclusion, the present study suggests that Capric acid decreases PGE2 production by inhibition of enzymatic conversion and by reduction of substrate availability for COX-2. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T01:07:55Z (GMT). No. of bitstreams: 1 ntu-96-R94b47307-1.pdf: 1047813 bytes, checksum: 33fd36a147296fc15e95240ac71aeffe (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 目錄 i
圖表目錄 iii 縮寫對照表 v 摘要 vi 中文摘要 vii 第一章 緒言 1 第一節 前言 1 第二節 文獻回顧 2 一、前列腺素E2（PGE2）的介紹 2 (一) 前列腺素E2 的生合成 2 (二) 前列腺素合成酶 (PGHS) 4 二 巨噬細胞的介紹 7 (一) 巨噬細胞的活化 7 (二) 脂多醣類(LPS：Lipopolysaccharide)的結構 7 (三) LPS活化巨噬細胞的傳訊路徑 8 (1) LPS結合蛋白(LPS binding protein：LBP)與LPS 結合受體 8 (2) 訊息傳遞(signal transduction) 10 三、癸酸的介紹 13 第三節 動機與目的 14 第二章 材料與方法 15 第一節 前言 15 第二節 細胞培養 15 一 細胞培養系統 15 （一）細胞來源 15 （二）細胞處理流程 15 （1）Capric acid 對LPS誘導PGE2生成之影響 15 （2）癸酸預處理或後處理對LPS誘發發炎反應的影響 16 （3）癸酸對COX-2（Cyclooxygenase-2）蛋白質表現量的影響 16 (3A) 癸酸處理對COX-2蛋白質表現量的影響 16 (3B）改變癸酸的處理時間、濃度對於COX-2表現量的影響 17 （4）給予基質AA，探討癸酸對AA獲取的影響 18 二 細胞培養用試劑與器材 18 第三節 生物活性分析 20 一 細胞存活率--- MTT之測定 20 二 前列腺素E2 (Prostaglandin E2, PGE2) 的測定 21 三 COX-2蛋白質表現量測定 23 （一）細胞溶解與蛋白質萃取 23 （二）測定蛋白質濃度 24 （三）電泳與免疫轉印 25 四 COX (cyclo-oxygenase) 的 peroxidase 活性測定 30 五 COX-2活性測定 30 六 Maximum inhibition(%)及IC50的計算 32 第四節 統計分析 33 第三章 結果 34 第一節 癸酸與LPS共處理對RAW264.7細胞PGE2的影響 34 （一）癸酸抑制LPS刺激 RAW264.7 產生PGE2 34 （二）癸酸不影響 COX-2 蛋白質的表現 34 第二節 癸酸與 LPS 處理順序對 LPS 誘發 PGE2 生成的影響 39 （一）先以 LPS 誘發 PGE2 生成，再以癸酸處理 39 （二）先以癸酸預處理，再以LPS刺激發炎反應 40 第三節 外源性 AA 對於癸酸抑制的影響 47 第四章 討論 59 第一節 癸酸與LPS共處理對細胞的影響 59 第二節 癸酸與LPS處理順序對 LPS 誘發PGE2的影響 60 第三節 外源性 AA 對於癸酸抑制的影響 61 第四節 展望 63 總結 64 參考文獻 65 | |
| dc.language.iso | zh-TW | |
| dc.subject | 發炎 | zh_TW |
| dc.subject | 癸酸 | zh_TW |
| dc.subject | 前列腺素E2 | zh_TW |
| dc.subject | inflammation | en |
| dc.subject | PGE2 | en |
| dc.subject | capric acid | en |
| dc.title | 癸酸降低脂多醣活化巨噬細胞株前列腺素E2生成之機制探討 | zh_TW |
| dc.title | Capric Acid Inhibits the Production of PGE2 by LPS-Activated Macrophage Cell Line | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 宋賢一,黃永勝,林璧鳳,吳文惠 | |
| dc.subject.keyword | 癸酸,發炎,前列腺素E2, | zh_TW |
| dc.subject.keyword | capric acid,inflammation,PGE2, | en |
| dc.relation.page | 73 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-23 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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