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研究生:賴俊利
論文名稱:探討CDK抑制劑抑制LPS誘導macrophagecell發炎反應之作用機制
論文名稱(外文):CDK inhibitors, olomoucine and roscovitine, reduce pro-inflammatory responses
指導教授:唐世杰
指導教授(外文):Tang Shye-Jye
學位類別:碩士
校院名稱:國立海洋大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
中文關鍵詞:發炎
外文關鍵詞:olomoucineroscovitine
相關次數:
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中文摘要
發炎反應原本是身體的自我保護機制,但是過度的發炎反應也會造成身體的不適,如發燒、頭痛、痛風、關節炎、過敏等症狀。當巨噬細胞受到內毒素脂多醣LPS(lipopolysaccharide)或免疫刺激(Interferon-gamma, IFN-γ)時,會產生各種發炎調節因子,誘發一系列的發炎反應。在本研究中,我們以內毒素脂多醣LPS (lipopolysaccharide) 去處理RAW264.7 cells,模擬發炎反應,探討 CDK inhibitor olomoucine 及 roscovitine可能會調節巨噬細胞發炎的調節因子釋放程度及相關調控基因的影響。實驗中我們發現,olomoucine和roscovitine以劑量相關的方式抑制 LPS 所誘發之 iNOS mRNA表現、蛋白質表現、promoter的活性及NO釋放。在MAPKS訊號傳遞路徑的探討上,我們發現P38抑制劑 (SB203580)、JNK抑制劑 (SP600125)也會抑制LPS 所誘發之NO的釋放,表示LPS 所誘發之NO釋放部份經由P38與JNK活化的訊號傳遞路徑。同時處理CDK inhibitor及MAPKS inhibitor 時,發現CDK inhibitor對LPS 所誘發之發炎反應的調節作用,也會透過P38與JNK活化的路徑。綜合以上的結果得知,在RAW264.7 巨噬細胞中,LPS 可經由P38 MAPK 及JNK二條訊號傳遞路徑,調控NO的釋放,且olomoucine和roscovitine對LPS 所誘發之發炎反應的調節作用也會透過P38 MAPK 及JNK二條訊號傳遞路徑。
第一部分
中文摘要
英文摘要
壹、序論……………………………………………………………………1
1.Macrophage 細胞生理的功能………………………………………...1
2.巨噬細胞的活化……………………………………………………….3
3.LPS產生的發炎反應之訊號傳遞…………………………………….3
4.NO與發炎反應………………………………………………………..5
5.細胞週期的調控……………………………………………………….6
6.細胞週期抑制劑……………………………………………………….7
7.實驗目的……………………………………………………………….8
貳、實驗材料………………………………………………………………9
參、實驗方法……………………………………………………………...13
1.(MTS)細胞數測定…………………………………………………13
2. RNA純化…………………………………………………………..…14
3.反轉錄反應(Reverse Transcription, RT)…………………………..14
4.聚合酵素連鎖反應(Polymerase chain reaction, PCR)……………15
5. 細胞破碎……………………………………………………………..18
6. SDS-PAGE………………………………………….…………………19
7.西方點墨法(Western blotting)……………………………………..21
8.Transfection…………………………………………………………….22
9.細胞分化測定( Flow cytometry — PI cell cycle )……………………...23
肆、結果……………………………………………………………………24
1.LPS誘導細胞發炎的能力…………………………………………….24
2.olomoucine與roscovitine抑制細胞生長的能力…………………….24
3.olomoucine、roscovitine不會造成細胞凋亡………………………...24
4.olomoucine、roscovitine具有調節LPS誘導之細胞發炎的能力…..25
5.olomoucine、roscovitine 具有調節NO誘導細胞發炎能力之dose-dependent分析…………………………………………………..25
6.olomoucine、roscovitine調節iNOS mRNA、iNOS蛋白質及NO
氣體的產生…………………………………………………………...26
7.olomoucine、roscovitine 調節 iNOS promoter 的活性……………27
8.olomoucine、roscovitine調節NO誘導細胞發炎的能力透過活化 P38、JNK,而不透過活化PI3K、ERK途徑…………………………….27
伍、討論…………………………………………………………………...29
陸、參考文獻……………………………………………………………...32
柒、附圖……………………………………………………………………48
第二部分
中文摘要
英文摘要
壹、 序論……………………………………………………………………66
貳、 實驗材料與方法………………………………………………………72
參、 結果……………………………………………………………………78
肆、 討論…………………………………………………………………... 79
伍、 參考文獻……………………………………………………………... 80
陸、 附圖……………………………………………………………………87
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