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研究生:詹于瑩
研究生(外文):Yu Ying Chan
論文名稱:棕櫚酸和棕櫚油酸影響人類嗜中性白血球釋放超氧自由基和彈性蛋白酶的機轉探討
論文名稱(外文):Role of Palmitic Acid and Palmitoleic Acid on Superoxide Anion and Elastase Release in Human Neutrophils
指導教授:黃聰龍黃聰龍引用關係
指導教授(外文):T. L. Hwang
學位類別:碩士
校院名稱:長庚大學
系所名稱:天然藥物研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
論文頁數:73
中文關鍵詞:嗜中性白血球棕櫚酸棕櫚油酸
外文關鍵詞:neutrophilspalmitic acidpalmitoleic acid
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研究報告顯示,棕櫚酸palmitic acid (PA)和棕櫚油酸palmitoleic acid (POA)影響生理功能而與代謝疾病具有相關性。儘管知識的進展,PA和POA調節人類嗜中性白血球的生理功能仍未瞭解。本論文結果顯示,POA有濃度相關性的抑制formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)誘發人類嗜中性白血球超氧自由基的生成和彈性蛋白酶的釋放,但是PA則沒有此現象。POA不具有抗氧化作用或清除O2.- 的能力,並且不會直接抑制彈性蛋白酶的活性。POA會增加以FMLP刺激人類嗜中性白血球下細胞內cAMP的含量。特別的是,protein kinase A抑制劑H89會部份逆轉POA抑制超氧自由基生成的作用,而不會影響其抑制顆粒釋放的作用。這個結果顯示,POA經由cAMP-dependent路徑抑制超氧自由基的生成及cAMP-independent路徑抑制彈性蛋白酶的釋放。再者,將嗜中性白血球處理在有鈉或無納的緩衝液,以FMLP刺激,POA會降低鈣離子濃度,此現象會被H89部份逆轉;不過,POA並不會抑制thapsigargin所誘導的細胞外鈣內流的現象。另外,在FMLP刺激下,POA抑制細胞外鈣內流,但是不會抑制鋇離子濃度變化,這個結果顯示,POA的抑制功能不是經由抑制store-operated channel而來。另一方面,POA會抑制A23187刺激所造成的細胞內鈣離子濃度上升的作用,但是PGE1和rolipram沒有此現象,而且POA的抑制作用不會被H89所逆轉。綜合上述結果顯示,POA會經由cAMP-dependent和cAMP-independent路徑而抑制鈣離子,進而分別抑制人類嗜中性白血球釋放超氧自由基及彈性蛋白酶。這些結果也發現PA和POA調節嗜中性白血球發炎反應的差異。
There are considerable evidences that palmitic acid (PA) and palmitoleic acid (POA) affect several important physiologic functions relating to the development of metabolic syndrome. In spite of the progress of knowledge, the physiological role of PA and POA in regulating neutrophil functions remains poorly understood. In this study, our data showed that POA, but not PA, inhibited superoxide anion (O2.-) and elastase release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated human neutrophils in a concentration-dependent fashion. POA did not display antioxidant or O2.--scavenging ability and it could not directly inhibit the activity of human neutrophil elastase. The cAMP levels were increased by POA in the FMLP-activated human neutrophils. Specially, the inhibitory effect of POA on superoxide generation, but not elastase release, was reversed by the protein kinase A inhibitor, H89, suggesting that POA-caused inhibition of O2.- generation and elastase release was via cAMP-dependent and -independent pathways, respectively. Furthermore, POA significantly reduced calcium mobilization induced by FMLP, but not by thapsigargin, in both normal and sodium-deprived media, which was partially reversed by H89. In addition, POA inhibited extracellular calcium, but not barium entry, in FMLP-activated human neutrophils, suggesting that the inhibitory function of POA was not through the inhibition of store-operated Ca2+ channel. On the other hand, calcium ionophore A23187 induced calcium influx was reduced by POA, but not by PGE1 and rolipram, and the inhibitory effect of POA was not inhibited by H89. In summary, these results indicate that the suppressive effects of POA on human neutrophil respiratory burst and degranulation are mediated by cAMP-dependent and -independent inhibitions of calcium mobilization. Also, these findings suggest an important discrepancy between the functions of POA and PA in neutrophilic inflammation.
緒論..................1
實驗材料與方法........12
結果.................17
討論.................22
圖表.................26
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