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研究生:吳弦璞
研究生(外文):Sian Pu Wu
論文名稱:牛樟芝酒精萃取液藉由抑制NLRP3發炎小體路徑活化進而減緩發炎細胞激素IL-1β與IL-18的分泌
論文名稱(外文):Antrodia cinnamomea ethanol extract suppresses interleukin-1β and interleukin-18 secretion by inhibiting the NLRP3 inflammasome activation pathway
指導教授:賴信志賴信志引用關係
指導教授(外文):H. C. Lai
學位類別:碩士
校院名稱:長庚大學
系所名稱:醫學生物技術暨檢驗學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
論文頁數:47
中文關鍵詞:介白素-1beta介白素-18NLRP3發炎小體牛樟芝抗發炎
外文關鍵詞:IL-1 betaIL-18NLRP3 inflammasomeAntrodia CinnamomeaAnti-inflammation
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牛樟芝在台灣一直以來都是民間療法的藥材,先前已有報導指出牛樟芝可透過不同的分子機制達成各式治療效果,例如:抗癌、抗高血壓以及免疫調控…等功能。雖有免疫調控方面的報導,但是牛樟芝與發炎小體之間的關係卻尚未被提及。於本實驗中,結果顯示出牛樟芝酒萃液可明顯地抑制受LPS及ATP刺激後的人類THP-1巨噬細胞中前發炎細胞激素IL-1β和IL-18的生成。牛樟芝酒萃液的前處理也能抑制caspase-1的活化以及參與在NLRP3發炎小體活化路徑中的成分蛋白NLRP3的生成。此外,牛樟芝酒萃液也能抑制P2X7受器的表現及活性氧(ROS)的生成。依據本實驗結果可以確定牛樟芝可透過調控發炎小體的活化進而抑制前發炎細胞激素IL-1β以及IL-18的分泌,達到抑制發炎反應發生的功效。
The extracts of Antrodia cinnamomea has long been used as a traditional Chinese medicine. Previous studies have showed that A. cinnamomea extracts exhibits many pharmacological properties, such as anti-cancer, anti-hypertensive and anti-inflammatory activities. Although A. cinnamomea extracts are reported to possess the anti-inflammatory activity, the effects of A. cinnamomea ethanol extract (ACEE) on the production of pro-inflammatory cytokine IL-1β and IL-18, and the regulation of the inflammasome pathway have not been clearly elucidated yet. In the present study, ACEE markedly suppresses the secretion of IL-1β and IL-18 in LPS-primed and ATP-stimulated macrophages. ACEE pre-treatment also results in a significantly reduction of ATP-induced caspase-1 activation. Moreover, we observed that ACEE not only inhibits the expression of NLRP3, and the purinergic receptor, P2X7R, but also reduces reactive oxygen species (ROS) production. Taken together, these findings indicate that ACEE reduces the secretion of IL-1β and IL-18 through the regulation of the NLRP3 inflammasome pathway to achieve the anti-inflammatory effect.
指導教授推薦書
口試委員審定書
長庚大學授權書......................................................................... III
誌謝........................... ...................................................... IV
中文摘要............................................................................... VI
Abstract............................................................................. VII
Contents............................................................................. VIII
Chapter 1: Introduction.......................................................................... 1
1.1 Antrodia Cinnamomea............................................................... 1
1.2 Inflammasomes..................................................................... 3
1.3 Aim of this study................................................................. 7
Chapter 2: Materials and Methods...................................................... 8
2.1 Chemicals and reagents............................................................ 8
2.2 Cell culture and treatments....................................................... 9
2.3 Cell viability assay............................................................. 10
2.4 Enzyme-linked immunosorbent assay (ELISA)........................................ 10
2.5 Protein extraction and Western blot analysis..................................... 11
2.6 RNA isolation and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis ..................................................................................... 12
2.7 Quantitative real-time PCR analysis.............................................. 13
2.8 Measurement of ROS production.................................................... 14
2.9 Statistical analysis............................................................. 15
Chapter 3: Results.............................................................................. 16
3.1 Effect of ACEE on cell viability in human THP-1 macrophages...................... 16
3.2 Pretreatment of ACEE inhibits ATP-mediated IL-1β and IL-18 secretion in human macrophages ......................................................................... 16
3.3 Pretreatment of ACEE inhibits ATP-mediated caspase-1 activation in human macrophages ..................................................................................... 17
3.4 Pretreatment of ACEE suppresses the expression of NLRP3.......................... 18
3.5 Pretreatment of ACEE suppresses the expression of purinergic P2X7 receptor ..................................................................................... 19
3.6 ACEE down-regulates ROS production in LPS-primed and ATP-stimulated macrophages ..................................................................................... 20
Chapter 4: Discussion........................................................................... 21
References........................................................................... 26
Appendix............................................................................. 30
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