研究生: |
李佳陽 LI, Chia-Yang |
---|---|
論文名稱: |
冬蟲夏草對人類樹突狀細胞在不同生理層次之免疫調節影響:從細胞生物學至基因體學研究 The immunomodulatory effect of Cordyceps sinensis on dendritic cells in different physiological stages : from cell biology to genomics study |
指導教授: |
許志楧
Hsu, Ian C. |
口試委員: | |
學位類別: |
博士 Doctor |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2010 |
畢業學年度: | 99 |
語文別: | 英文 |
論文頁數: | 87 |
中文關鍵詞: | 冬蟲夏草 、樹突狀細胞 、免疫調節 、基因晶片 |
外文關鍵詞: | Cordyceps sinensis, Dendritic cells, Immunoregulation, Microarray |
相關次數: | 點閱:4 下載:0 |
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中草藥在臨床上的運用已經累積了數千年的經驗。然而,以科學實驗的方法來驗證其對細胞或生物體的影響,仍處於起步階段。近年來,由於醫學科技的進步,中草藥科學化已經是時代的趨勢。為達到此一目標,首先要建立一套以科學實驗的方法,來評鑑中草藥在中醫典籍內所標示的療效。本研究主要針對中草藥對於免疫功能的影響做更深入的探討。樹突狀細胞是一種高效能的抗原呈獻細胞,其不僅有先天性免疫反應的功能,更具有活化及開啟後天性免疫反應的功用。因此,利用樹突狀細胞來做為研究中草藥的免疫調節機制十分恰當,其不僅可以評估先天性免疫的調節功效,對於引發專一性的後天性免疫反應之調節功效也可以評估。
本研究基於樹突狀細胞的特性,建立了一個免疫功能評估的分析平台,測試冬蟲夏草對於樹突狀細胞免疫功能的影響。在冬蟲夏草的部分,我們的實驗結果發現冬蟲夏草對未成熟的樹突狀細胞及脂多醣刺激樹突狀細胞成熟過程中具有雙向調節的作用,其可促使未成熟的樹突狀細胞成熟,並激活免疫反應,促進T細胞增生並使其發展偏向Th1細胞性免疫反應。相反的,我們利用脂多醣刺激樹突狀細胞成熟,同時我們加入冬蟲夏草刺激,結果我們發現冬蟲夏草會抑制脂多醣引發的過度免疫反應,抑制脂多醣促使樹突狀細胞成熟的反應,抑制脂多醣所造成的發炎反應,並抑制脂多醣引發的Th1細胞性免疫反應使其走向Th2體液性免疫反應。此外,我們也利用基因晶片進一步探討冬蟲夏草對於樹突狀細胞的作用機制,基因晶片的結果找到了許多參與免疫調節與發炎反應的基因,以及冬蟲夏草對於不同樹突狀細胞的生理層面所產生調控的特有基因群。我們的結果也指出冬蟲夏草在不同樹突狀細胞的生理層面所產生影響之可能的藥理機制。
The Chinese herbal medicine has been administered in traditional Chinese therapy for well over two thousand years. However, the pharmacological study of Chinese herbs on biological objects is still in its infancy. Modernization of Chinese medicine has provoked great interest among bio-medical researchers globally. In order to reach this goal, should set up a set of methods by scientific experiment first, to comment the Chinese herbal medicine curative effect labeled in the Chinese medicine ancient books and records. This study focuses on the effects of Chinese herbal medicine on the immunological function. Dendritic cells (DCs) are most potent antigen-presenting cells in the human body which involved in the regulation of both innate and adaptive immune responses. Based on its function, DCs can be used as therapeutic targets for investigating the immunomodulation of Chinese herbal medicine, not only estimating the innate immune response but also estimating the adaptive immune response.
This study is based on the characteristic of DCs to set up a platform for analyzing the immune function. We examined the effect of Cordyceps sinensis (CS) on dendritic cells in different physiological stages respectively. In the results of CS, CS can exert differential immunomodulatory effects on DCs upon different physiological states, naïve-stage DCs and LPS-activated DCs. Our experimental results demonstrate that CS activates immature DCs and enhances immature DCs maturation, increases proinflammatory cytokine secretion by DCs, and promotes T cell proliferation and Th1 polarization. On the other hand, CS suppresses the LPS-induced inflammatory response by decreasing the LPS-induced DC maturation, inhibiting proinflammatory cytokine secretion by DCs, reducing the LPS-activated DC-elicited allogeneic T cell proliferation, and shifting the LPS-activated DC-driven Th1 response toward a Th2 response. Additionally, we further examine the effective mechanisms of CS on DCs using microarray technology. By the results of cDNA microarray, we found several immunoregulation-related genes and inflammation-related genes. Furthermore, we classified the unique genes that specific regulated by CS treatment on DCs upon different physiological states. Our results indicate the possible pharmacological mechanisms mediated by CS on DCs at different stages.
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