記錄
編號
5426
狀態
NC093FJU00105009
助教
查核
索書
號
學校
名稱
輔仁大學
系所
名稱
生命科學系
舊系
所名
稱
學號
492546032
研究
黃敏瑜
生(中)
研究
Huang Min Yu
生(英)
論文
名稱
(中)
靈芝蛋白 LZ-8 抗發炎活性的探討
論文
名稱
(英)
The study of a Ling Zhi protein, LZ-8, on anti-inflammatory responses
其他
題名
指導
教授
(中)
周秀慧
指導
教授
(英)
Chou Shiu-Huey
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學位
類別
碩士
畢業
學年
度
93
出版
年
語文
別
中文
關鍵
靈芝蛋白,抗發炎
字(中)
關鍵
LZ-8, anti-inflammatory responses
字(英)
摘要
(中)
中文摘要 LZ-8（Ling Zhi-8，LZ-8）是由靈芝（Ganoderma lucidium）菌絲
體萃取出來具免疫調節功能的蛋白質。先前體外細胞實驗發現 LZ-8 能
促進小鼠脾臟細胞及人類周邊血液 T 淋巴細胞增生，而 LZ-8 在活體動
物實驗能有效抑制小鼠全身過敏性反應（Systemic Anaphylaxis Reaction）
或非肥胖型糖尿病鼠（non-obese diabetic（NOD）mice）第一型糖尿病
（Insulin-dependent diabetes mellitus, IDDM）之發生，還可降低接受同種異
體移植小鼠所引起的免疫排斥現象。近年來研究顯示急性或持續性的發
炎反應可造成許多疾病的發生，例如自體免疫疾病、敗血症和動脈粥狀
硬化等，因此，開發抗發炎藥物是目前生物醫學研究主要課題之一。本
研究目的主要是評估 LZ-8 是否可影響發炎反應，以期開發作為有效的
抗發炎藥物。本研究使用的 LZ-8 是利用麵包酵母菌表現載體導進，並
配合發酵技術以大量培養，經過純化與活性測定篩選而得的，再將 LZ-8
分別與受到活化的小鼠巨噬細胞株或老鼠腹腔沖出細胞作用，評估其對
發炎相關物質表現的影響，以及進一步的以活體發炎模式評估其抗發炎
的功效。結果發現 LZ-8 在不影響細胞存活率的濃度下，能夠有效的抑
制受 LPS（Lipopolysaccharides）與 IFN-γ（Interferon-γ）活化的小鼠巨
噬細胞株 RAW264.7 產生 NO（IC50 = 1.057 μg/ml）和 IL-6。並以西方墨
點法分析發現 LZ-8 可抑制巨噬細胞株中 NO 合成的 inducible nitric oxide
synthase（iNOS）的表現，由此推測 LZ-8 對抑制細胞 NO 的生成與 iNOS
的表現有關。再以受 LPS 與 IFN-γ 活化的小鼠腹腔?出細胞（PEC）與
LZ-8 共同作用，同樣發現 LZ-8（1 μg/ml）能有效抑制細胞產生 NO、
TNF-α 及 IL-6 等發炎物質。發炎活體動物實驗的結果則顯示，接受 LZ8（10 mg/kg 小鼠體重）腹腔注射可明顯減弱小鼠 LPS 注射所引發血清
中 IL-6、IL-1β 與 TNF-α 的上升，也可以減弱小鼠 LPS 注射所引發腹
腔沖出細胞 IL-1β、IL-6、TNF-α 上升並降低 IL-10 產生，另外，LZ-8
可增加健康小鼠脾臟與胸腺 T 細胞的增殖活性，但並不影響發炎小鼠脾
臟與胸腺免疫的活性。綜合以上結果得知，靈芝中 LZ-8 具有減緩發炎
作用的功效。
摘要
(英)
Abstract Ling Zhi-8 (LZ-8) is a glycoprotein purified from the mycelial extracts of
Ganoderma lucidum and has immunodulatory capacities. It has been reported that
LZ-8 exhibited mitogenic activity on mouse splenocytes and human peripheral
blood mononuclear cells in vitro and immunosuppressive in vivo by reducing
HBsAg-specific antibody production, by preventing the incidence of autoimmune
diabetes in non-obese diabetic mice, and by delaying the rejection process of
allogeneic islets transplantation. Accumulating data recently indicated that the
incidences of many diseases, such as autoimmune disease, sepsis, and
atherosclerosis, are related with the occurrence of persistence inflammatory
responses. Therefore, the development of a novel anti- inflammatory drugs is one
of the major goals on biomedical research. The purpose of this study is estimated
the anti-inflammatory effects on LZ-8 protein. LZ-8 proteins were produced used
a baker yeast (Saccharomyces cerevisiae) expression system. The concentration
and bioactivity were determined before used in the experiment. Both macrophage
cell line (RAW 264.7) and peritoneal excudated cell (PEC) were first used to
evaluate the anti-inflammatory effect in vitro, and a LPS-induced inflammatory
mouse model was further used to estimate the anti-inflammation in vivo. Results
indicated that LZ-8 suppressed the nitric oxide (NO) and interleukin-6 (IL-6)
production from RAW 264.7 cells after LPS and IFN-γstimulation. With
Western-blot analysis, LZ-8 also inhibited the protein production of iNOS, a
inducible nitric oxide synthase. Moreover, LZ-8 also suppressed NO, TNF-α, and
IL-6 production in mice peritoneal excudated cells with LPS and IFNγstimulation. The results of animal study indicated that LPS-induced the increase
of IL-1β, IL-6, and TNF-αin serum and PEC were attenuated in mice which
received LZ-8 injection. As well, LZ-8 decreased the production of IL-10 in PEC.
In addition, LZ-8 administration could enhance the mitogenic activities of T cells
in spleen and thymus of healthy mice, however, LZ-8 did not affect the change of
immune activities in spleen and thymus of LPS-injected mice. In summary, LZ-8
from Ling Zhi posses the anti-inflammatory effects.
論文
目次
參考
文獻
目錄 中文摘要 英文摘要 第一章 前言 第二章 研究背景 第一節 發炎反應
第二節 天然物與抗發炎的研究報告 第三節 靈芝蛋白(Ling Zhi protein,LZ8)的研究背景 第三章 研究目的與重要性 第四章 實驗材料與方法 第一節
實驗設計 第二節 實驗材料 第三節 儀器設備 第四節 實驗方法 第五章 結
果 第一節 LZ-8 對 LPS/IFN-?活化的小鼠巨噬細胞株的影響 第二節 LZ-8
對 LPS/IFN-?活化的小鼠腹腔沖出細胞的影響 第三節 LZ-8 對發炎小鼠的
影響評估 第六章 討論 第七章 總結 第八章 參考文獻 附表 表一、天然物
之萃取物抗發炎的效用 表二、靈芝的主要藥理成分及生理功能 表三、
LZ-8 注射對發炎模式小鼠血清、腹滲液和腹腔沖出細胞中發炎 細胞激
素之影響 表四、LZ-8 注射對發炎模式小鼠腹滲液、腹腔沖出細胞、脾
臟細胞中 一氧化氮之影響 附圖 圖一、LZ-8 對 LPS/IFN-γ 活化小鼠巨噬
細胞株釋放 NO 的影響 圖二、LZ-8 對 LPS/IFN-γ 活化小鼠巨噬細胞株
細胞存活率的影響 圖三、LZ-8 對 LPS/IFN-γ 活化小鼠巨噬細胞株一氧
化氮合成?(iNOS) 蛋白質表現量的影響 圖四、LZ-8 對 LPS/IFN-γ 活化小
鼠巨噬細胞株釋放 TNF-α 的影響 圖五、LZ-8 對 LPS/IFN-γ 活化小鼠巨
噬細胞株釋放 IL-6 的影響 圖六、LZ-8 對 LPS/IFN-γ 活化小鼠巨噬細胞
株釋放 PGE2 的影響 圖七、LZ-8 對 LPS/IFN-γ 活化小鼠腹腔沖出細胞釋
放 NO 的影響 圖八、LZ-8 對 LPS/IFN-γ 活化小鼠腹腔沖出細胞細胞存
活率的影響 圖九、LZ-8 對 LPS/IFN-γ 活化小鼠腹腔沖出細胞釋放 TNFα 的影響 圖十、LZ-8 對 LPS/IFN-γ 活化小鼠腹腔沖出細胞釋放 IL-6 的
影響 圖十一、LZ-8 對 LPS/IFN-γ 活化小鼠腹腔沖出細胞釋放 PGE2 的影
響 圖十二、LZ-8 注射對發炎模式小鼠血中各類白血球含量之影響 圖十
三、LZ-8 注射對發炎模式小鼠活化的腹腔細胞 PGE2 分泌量之影響 圖十
四、LZ-8 注射對發炎模式小鼠腹腔細胞 IL-10 分泌量之影響 圖十五、
LZ-8 注射對發炎模式小鼠脾臟細胞培養上清液中 IL-1β?濃度之 影響 圖
十六、LZ-8 注射對發炎模式小鼠脾臟細胞培養上清液中 IL-6 濃度之 影
響 圖十七、LZ-8 注射對發炎模式小鼠脾臟細胞與 LPS 或 LZ-8 共同培養
上清液中 TNF-α 濃度的影響 圖十八、LZ-8 注射對發炎模式小鼠脾臟細
胞與 Con A 或 LZ-8 共同培養 上清液中 IFN-γ 分泌量的影響 圖十九、
LZ-8 注射對發炎模式小鼠脾臟細胞以 Con A 或 LPS 活化增生 之影響 圖
二十、LZ-8 注射對發炎模式小鼠胸腺細胞以 Con A 活化增生之影響
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