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研究生:許嘉偉
論文名稱:由五倍子純化之1,2,3,4,6-Penta-O-galloyl-b-D-glucose抑制人類周邊血單核細胞活化與增生訊息
論文名稱(外文):Activation and Proliferation Signals in Human Peripheral Blood Mononuclear Cells Inhibited by 1,2,3,4,6-Penta-O-galloyl-b-D-glucose Isolated from Galla chinensis
指導教授:郭育綺郭育綺引用關係
學位類別:碩士
校院名稱:輔仁大學
系所名稱:生命科學系碩士班
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:73
中文關鍵詞:12346-Penta-O-galloyl-b-D-glucose五倍子人類周邊血單核細胞植物凝集素
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五倍子(Galla chinensis)為漆樹科(Anacardiaceae)植物鹽膚木(Rhus chinensis Mill.)、青麩楊(Rhus potaninii Maxim.)或紅麩楊(Rhus punjapabensis Steward var. sinica (Diels) Rehd. et Wils.)之組織經由角倍蚜(Melaphis chinensis (Bell) Baker)及倍蛋蚜(Melaphis paitan Tsai et Tang)寄生後而形成的蟲癭(Insect gall),自古以來被中醫界作為收斂、止血、止咳之藥方,而其中的有效成分1,2,3,4,6-Penta-O-galloyl--D-glucose(PGG, C41H32O26, M.W. 940)為一種五倍子鞣質(gallotannin),本實驗以此為材料,探討PGG對於人類周邊血單核細胞(Human peripheral blood mononuclear cells; PBMCs)活化與增生訊息之影響,實驗結果顯示:利用3H-Thymidine吸收檢測法,發現PGG可抑制由植物凝集素(Phytohemagglutinin; PHA)刺激所引起之人類周邊血單核細胞增生,其百分之五十抑制濃度(IC50)為7.43 M,而此抑制效果可存在於加藥時間在72小時內。進一步利用流式細胞儀(Flow cytometer)分析PGG對於PBMC細胞週期進行之影響,發現PGG可抑制由PHA刺激所發生的細胞週期進行,使細胞週期停留在G0/G1期。同時PGG也可顯著抑制細胞週期素(Cyclin)D3、E、A及B的生成。PGG可以顯著降低第二介白質(Interleukin-2; IL-2)、第十介白質(Interleukin-10; IL-10)、第四介白質(Interleukin-4; IL-4)甲種腫瘤壞死因子(Tumor necrosis factor-; TNF-)以及丙種干擾素(Interferon-, IFN-)等細胞激素(cytokine)之蛋白質及mRNA之產生。探尋PGG於訊息傳導之作用點,發現PGG可以抑制經PHA刺激後細胞內鈣離子濃度之提升。而偵測細胞內c-Jun NH2-terminal kinases(JNK)、extracellular signal-regulated kinases(ERK)以及p38三種MAP kinase,發現PGG對於此三種MAP kinase的活化並沒有影響。本論文認為五倍子之免疫調節作用可能與下列活性有關:(1)PGG降低PHA所引起細胞內鈣離子之濃度;(2)PGG能降低IL-2 mRNA、IL-4 mRNA、IL-10 mRNA、IFN-γ mRNA及TNF- mRNA在活化PBMCs中之表現量。(3)PGG降低IL-2、IL-4、IL-10、IFN-γ、TNF-之基因表現,使得細胞激素產量減少。(4)PGG減少Cyclin D3、Cyclin E、Cyclin A與Cyclin B在活化細胞中的表現量;(8)PGG抑制細胞週期的進行,將細胞週期阻斷於G0/G1階段。此現象之阻斷可能與Cyclin D3、Cyclin E、Cyclin A與Cyclin B在活化細胞中的表現量降低有關;及(9)由實驗中觀察到PGG抑制活化之 PBMCs 增生。
Galla chinensis is traditionally used in Chinese medicine for long lasting cough and for arresting bleeding. Action mechanisms of 1,2,3,4,6-Penta-O-galloyl-b-D-glucose (PGG, C41H32O26, M.W. 940) isolated from Galla chinensis on phytohemagglutinin (PHA) stimulated cell proliferation were studied in human peripheral blood mononuclear cells (PBMCs). The results demonstrated that PGG suppressed PBMCs proliferation, at about 0 to 72 hr after stimulation with PHA. Cell cycle analysis indicated that PGG arrested cell cycle progression of activated PBMCs at G0/G1 phase. To elucidate the specific site of inhibition, some key components which promote proliferation were examined, including the expression and production of cytokines and cyclins, mobilization of intracellular Ca2+ ([Ca2+]i), phosphorylation of mitogen-activated protein (MAP) kinases. PGG supressed the production and mRNA expression of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), and tumor necorsis factor-alpha (TNF-alpha). PGG inhibited the production of Cyclin D3, Cyclin E, Cyclin A, and Cyclin B in PHA-stimulated PBMCs as well. Moreover, PGG reduced [Ca2+]i in PBMCs induced by PHA. PGG did not affect the activation of MAP kinases. The inhibitory effects of PGG appeared to be mediated, at least in part, through reduction of [Ca2+]i , cytokines and cyclins production, cell cycle progression and then PBMCs proliferation was suppressed.
壹、緒言 1
貳、材料與方法 6
參、結果 17
肆、討論 29
伍、參考文獻 35
表 39
圖 41
附圖 65
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