臺灣博碩士論文加值系統

巨噬細胞是具有高吞噬性功能的細胞，全身廣泛散佈，在宿主體內扮演著調控先天性免疫和發炎反應的重要角色。

巨噬細胞表面有細菌脂多醣（LPS）的接受體，利用LPS誘發產生的一氧化氮可以反應發炎之程度，並可用以評估藥物對於發炎過程的影響。

香芹酚（Carvacrol）為到手香中的主要成份，在許多研究中已證實香芹酚具有抗細菌、抗真菌以及殺蟲的效果，但卻少有文獻對於香芹酚之抗發炎效果進行討論。

初步實驗中，以體外試驗進行LPS對巨噬細胞產生發炎及香芹酚抗發炎效果之探討。在香芹酚的毒性測試中，發現香芹酚低於200μＭ時，對細胞並無明顯毒性。在NO測試中，先以最大LPS濃度(1μg/ml)誘導RAW264.7巨噬細胞產生發炎反應，再加入不同濃度之香芹酚，發現香芹酚有抑制NO產生的效果，在西方墨點法實驗中，iNOS和COX-2隨著

香芹酚濃度提升而下降，更進一步探討香芹酚消炎機制，發現隨著香芹酚濃度增加，IκB蛋白有被抑制磷酸化降解之作用，NF-κB無法進入核內，故證實香芹酚確實具有抗發炎之作用。

關鍵字：香芹酚、一氧化氮、前列腺素、發炎、巨噬細胞

Macrophages are phagocytic cells widely distributed throughout the body, and play essential role in innate immunity and inflammatory responses.

The macrophage surface has bacterial lipopolysaccharide (LPS) receptor. Nitric oxide (NO) production induced by LPS through iNOS (inducible NO synthase) induction may reflect the degree of inflammation and may provide a measure to assess the effect of drugs on the inflammatory process.

Main components of Plectranthus amboinicus is carvacrol. In this study, we attempt to investigate the effect of carvacrol on anti-inflammation in vitro. In the MTT assay, carvacrol has no cell toxicity on RAW264.7 cell up to 200μＭ. In the NO assay, RAW264.7 cell were treated with LPS (1μg/ml) and added with different concentration of carvacrol . Carvacrol was found to be the inhibitor of NO production and this effect was concentration-dependent.
In the western blotting experiment, iNOS and COX-2 were found to be attenuated by different concentrations of carvacrol.

This study suggests that inhibition of NO production in RAW264.7can be inhibited by carvacrol.

Key words: Carvacrol, NO, PGs, inflammation, macrophage

目錄
摘要............................................................................I
ABSTRACT........................................................................................................III
謝誌.......................................................................................................................V
目錄.....................................................................................................................VI
圖表目錄...........................................................................................................VIII
第1章 前言...........................................................................................................1
第2章 文獻回顧...................................................................................................3
2.1 到手香（PLECTRANTHUS AMBOINICUS）..........................................3
2.2 免疫反應............................................................................................6
2.3 巨噬細胞 (MACROPHAGE)................................................................6
2.4 發炎反應............................................................................................7
2.5 脂多醣（LIPOPOLYSACCHARIDE, LPS）...........................................8
2.6 一氧化氮（NITRIC OXIDE, NO）....................................................11
2.7 一氧化氮合成酶（NITRIC OXIDE SYNTHASE , NOS）...................14
2.8 環氧化酵素- 2 (CYCLOOXYGENASE-2, COX-2)...............................15
2.9 活性氧物質（REACTIVE OXYGEN SPECIES , ROS）........................18
2.10 血紅素氧化酶（HEME OXYGENASE-1 , HO-1）...........................22
第3章 材料與方法.............................................................................................24
3.1 研究目的 （AIM OF EXPERIMENT）...............................................24
3.2 實驗架構..........................................................................................25
3.3 細胞株 (CELL LINE).........................................................................26
3.4 儀器設備..........................................................................................26
3.5 藥品試劑..........................................................................................26
3.5.1 標準品....................................................................................26
3.5.2 抗體........................................................................................27
3.5.3 常用藥品................................................................................27
3.6 細胞解凍..........................................................................................29
3.7 細胞繼代培養..................................................................................29
3.8 細胞計數..........................................................................................29
3.9 細胞存活率分析（MTT assay）....................................................29
3.10 Nitrite 測定與分析.........................................................................30
3.11 蛋白質電泳與西方墨點法............................................................31
3.11.1 蛋白質萃取..........................................................................31
3.11.2 蛋白質定量..........................................................................32
3.11.3 蛋白質電泳分析..................................................................33
3.11.4 轉印與免疫染色法..............................................................35
3.12 細胞內ROS產量之分析................................................................37
第4章 結果與討論.............................................................................................38
4.1 細胞存活率偵測分析（MTT assay）...........................................38
4.2 Nitrite的測定與分析........................................................................38
4.3 ROS之測定.......................................................................................39
4.4 iNOS 酵素蛋白分析........................................................................40
4.5 COX-2蛋白質量分析.......................................................................41
4.6 HO-1蛋白質量分析..........................................................................42
4.7 IκB蛋白質量分析............................................................................43
第5章 討論.........................................................................................................64
第6章 結論.........................................................................................................67
參考文獻.............................................................................................................68
作者簡介.............................................................................................................81
圖表目錄
圖 1、 到手香..................................................................................................4
圖 2、 香芹酚結構..........................................................................................4
圖 3、 革蘭式陰性菌細胞壁外膜組成份......................................................8
圖 4、 ESCHERICHIA COLI 上LPS的結構......................................................10
圖 5、 內毒素的脂多醣與動物細胞上的TLR-4作用.................................12
圖 6、 NO合成酶之催化作用.......................................................................12
圖 7、 NO與氧之化學變化...........................................................................13
圖 8、 一氧化氮對癌症形成之影響............................................................14
圖 9、細胞內誘導iNOS和COX-2表現之可能路徑.....................................17
圖 10、環氧化酵素下游路徑圖......................................................................18
圖 11、前發炎因子及氧化物刺激調控下游細胞訊息傳遞..........................19
圖 12、ROS對於腫瘤促進產生之影響...........................................................21
圖 13、NADPH 氧化酶活化作用...................................................................21
圖 14、細胞內簡易氧化及抗氧化系統..........................................................22
圖 15、血氧化酶催化血紅素成膽綠素及一氧化碳......................................23
圖 16、細胞存活率偵測分析..........................................................................45
圖 17、不同濃度之Carvacrol對LPS誘發RAW264.7巨噬細胞一氧化氮 產生之抑制..........................................................................................46
圖 18、不同時間使用LPS誘發ROS產生量之測量.......................................47
圖 19、不同濃度香芹酚對ROS產生量之影響..............................................48
圖 20、使用不同濃度香芹酚對以LPS誘發RAW264.7巨噬細胞之ROS產生量之測量..........................................................................................49
圖 21、不同時間點LPS刺激RAW264.7細胞之iNOS蛋白質表現................50
圖 22、不同濃度香芹酚刺激RAW264.7之iNOS蛋白質表現量之影響...51
圖 23、不同濃度香芹酚對LPS刺激RAW264.7細胞之iNOS蛋白質............52
圖 24、同時間點LPS刺激RAW264.7細胞之COX-2蛋白質表現之影響.....53
圖 25、不同濃度香芹酚刺激RAW264.7之COX-2蛋白質表現量之影響....54
圖 26、不同濃度香芹酚對LPS刺激RAW264.7細胞之COX-2蛋白質現 量之影響..............................................................................................55
圖 27、不同時間點LPS刺激RAW264.7細胞之HO-1蛋白質表現................56
圖 28、不同濃度香芹酚刺激RAW264.7之HO-1蛋白質表現量之影響...57
圖 29、不同濃度香芹酚對LPS刺激RAW264.7細胞之HO-1蛋白質表現 量之影響..............................................................................................58
圖 30、不同時間點LPS刺激RAW264.7細胞之IκB蛋白質表現.................59
圖 31、不同濃度香芹酚刺激RAW264.7之IΚB蛋白質表現量之影響.....60
圖 32、不同濃度香芹酚對LPS刺激RAW264.7細胞之IκB蛋白質表現量之影響..................................................................................................61
圖 33、不同濃度香芹酚對LPS刺激RAW264.7細胞之P-IκB蛋白質表量之影響..................................................................................................62
圖 34、香芹酚對活化後RAW264.7 巨噬細胞內NFκB核轉移之影響...63
表 1、 香草植物精油中的香芹酚成分............................................................5
表 2、 香草精油用於加工食品........................................................................5
表 3、 一氧化氮合成酶之生物活性比較......................................................16
表 4、 主要的ROS分子與其代謝...................................................................20

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