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    標題: 大黃素對EB病毒腫瘤的影響
    Effects of emodin on EBV-associated tumor
    作者: 黃淨鈺
    貢獻者: 保健營養系
    林翠品
    關鍵字: Epstein-Barr 病毒
    大黃素
    丁酸鈉
    Epstein-Barr virus
    Sodium butyrate
    Emodin
    日期: 2017
    上傳時間: 2018-01-11 11:42:33 (UTC+8)
    摘要: Epstein-Barr病毒 (EBV) 是人類的皰疹病毒,與許多人類淋巴組織惡性腫瘤發生有關。先前實驗室研究發現,虎杖根部乙酸乙酯分離物F3a,藉由抑制NF-kB及ERK活化,使凋亡蛋白質caspase-3及PARP裂解增加,導致EB病毒腫瘤細胞走向凋亡。以逆向高效率液相層析儀分析發現虎杖乙酸乙酯分離物F3a主要成分為大黃素。因此本研究以動物模式探討大黃素是否能抑制帶有EB病毒腫瘤細胞的SCID小鼠之腫瘤增生,以及細胞學模式探討大黃素聯合丁酸鈉是否具有促進大黃素毒殺EB病毒腫瘤細胞的能力。在動物模式預防組實驗中以管餵方式將大黃素 (8.4及33.8 mg/kg bw/2day) 給予帶有EB病毒腫瘤細胞的SCID小鼠50天,結果發現存活率與肝臟中抗氧化酵素 (SOD、GPX、CAT、GSH、P450) 並沒有影響,也無法降低腫瘤體積與重量,但可以減少由EB病毒腫瘤細胞所引起相對脾臟重量的增加。而在治療組實驗中將大黃素 (8.4 mg/kg bw/2day) 直接注射於腫瘤部位,能減少腫瘤體積與重量。在細胞模式發現大黃素濃度45 M與丁酸鈉 (1.5或3 mM) 合併使用具有持續協同抑制EB病毒腫瘤細胞生長效果,並且作用能持續至72小時;而且能降低Raji細胞EBNA1 mRNA表現量,減少EB病毒DNA複製,抑制細胞增殖。也能增加BNLF1 mRNA表現量,減少IkBa磷酸化,進而抑制細胞增生;並且促進細胞內ROS表現量增加,使凋亡蛋白質caspase-3表現量及PARP裂解增加,使細胞凋亡。所以大黃素或大黃素與丁酸鈉合併使用具有開發成抗EB病毒相關腫瘤藥物的潛能。
    Epstein-Barr virus (EBV) is a human herpesvirus; that is associated with several human lymphoid malignancies. Our earlier study found that the ethyl acetate fraction F3a from Polygonum cuspidatum root promoted apoptosis of EBV-positive cells due to its ability to inhibit the NF-B and ERK activation and enhance the cleavage of apoptotic-related proteins, caspase 3 and PARP. The main component of the ethyl acetate fraction F3a was emodin, which identified by reverse-phase high performance liquid chromatography. Therefore, the purpose of this study is to investigate whether emodin can inhibit the tumor growth of SCID mice bearing EBV tumor cells and explore the effect for emodin with sodium butyrate to inhibit the growth of EBV-associated tumor cells. In prevention experiment, emodin (8.4 mg/kg bw/2 day and 33.8 mg/kg bw/2 day) were administered to SCID mice bearing EB virus tumor cells for 50 days. Researchults showed the survival rate and anti-oxidative enzyme (SOD, GPX, CAT, GSH, P450) of mice were not affected. The tumor volume and weight did not decrease, but spleen weight was reduced induced by the EBV-positive tumor cells. In the treatment experiment, emodin (8.4 mg/kg bw/2day) was injected directly into the tumor site, which reduced tumor volume and weight. In the cell model, 45 M emodin combined with sodium butyrate (1.5 or 3 mM) showed synergistic inhibition of EBV-positive tumor cell growth and the effect was sustained for up to 72 hours. The combination of emodin with sodium butyrate reduced the transcription of EBNA1, thus led to decrease of EBV DNA replication and inhibited cell proliferation. Meanwhile, the expResearchsion of BNLF1 mRNA expResearchsion was increased, which Researchult in the reduced phosphorylation of IkBa, exhibited intracellular reactive-oxygen species increasing, activation of apoptotic-related proteins, caspase-3 and cleavage of PARP and caused apoptosis. Therefore, emodin or emodin combined with sodium butyrate can be developed as a therapeutic drug in the treatment of EBV-related tumors.
    關聯: 大黃素對EB病毒腫瘤的影響
    顯示於類別:[保健營養系(所) ] 博碩士論文

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