臺灣博碩士論文加值系統

樟芝(Antrodia camphorata, Taiwanofungus camphoratus)為台灣特有種菇類，研究指出樟芝多醣體具有抗發炎、抗腫瘤的能力，顯示樟芝多醣體應具有調控免疫的功效，然而，在樟芝多醣體部分其如何調控免疫反應中的抗原呈獻細胞以及T細胞之相關作用及機制目前仍不清楚。就此，本實驗利用體外培養的小鼠骨髓衍生性樹突細胞來探討純化的樟芝多醣體（GF-2）對於樹突細胞的活化及T細胞的分化的影響。
結果顯示，GF-2會促進樹突細胞經由LPS刺激後所釋出的細胞激素IL-10與IL-12的生成量。另一方面，經由GF-2單獨刺激後的樹突細胞會大量表現CD80、CD86以及MHC class Ⅱ等細胞表面分子，然而，在GF-2合併LPS刺激下MHC class Ⅱ的表現量反而會下降。若進一步將刺激後的樹突細胞與T細胞共同培養，則GF-2將會抑制T細胞增生及細胞激素IL-4、IL-5的分泌，並促其分泌高量的IL-10。由以上體外實驗結果，我們推測GF-2藉由刺激樹突細胞分泌較多量的IL-10與降低MHC classⅡ表現量，來調控活化的T細胞分化成會分泌IL-10的T細胞群。在初步動物實驗方面，合併GF-2與過敏原OVA經由腹腔注射於小鼠體內，藉此探討GF-2能否成為免疫佐劑進而改變OVA造成的免疫反應。其結果顯示，GF-2能有效的降低血清中OVA專一性抗體IgG1與IgE的表現量。然而，GF-2能提升T細胞與B細胞的增生，且能明顯抑制IL-5的分泌並轉而提升IFN-γ與IL-10的生成。我們推測，樟芝多醣體可藉由促進Th1細胞激素IFN-γ與增加抗發炎細胞激素IL-10的分泌量來抑制Th2免疫反應。因此，我們進一步將樟芝多醣體應用於氣喘治療上。其結果顯示，GF-2能明顯減輕氣喘動物的呼吸道阻力，降低嗜酸性白血球在肺部的聚集，以及減少Th2細胞激素IL-4、IL-5、IL-13的生成量。總括而言，GF-2對於氣喘症狀有治療之功效，將來若能發展成為改善過敏體質之用藥，其對於過敏患者應是一大福祉。

Antrodia camphorata (syn. Taiwanofungus camphorata) is a special medicinal mushroom in Taiwan. Previous studies showed that polysaccharides isolated from Antrodia camphorata (AC-PS) had the anti-inflammation and anti-tumor abilities. However, the modulatory effects of AC-PS in antigen presenting cell (APC) and T cell are unclear. In this study, we first examined the immune-modulatory effects of the purified polysaccharides isolated from Antrodia camphorata (GF-2) on dendritic cells (DCs) and T cells. Our data showed that GF-2 enhanced the production of IL-10 and IL-12 from DCs challenged with LPS. GF-2 also increased the expression of CD80 and CD86 on DCs. However, GF-2 combined with LPS reduced the expression of MHC classⅡ. In addition, GF-2-treated DCs markedly drive T cells to develop into IL-10-secreting T cells. These results indicated that GF-2 promoted the production of IL-10 to modulate immune response in vitro. In vivo, mice were immunized with OVA plus GF-2 to investigate the modulatory effects of GF-2. Our data showed that GF-2 significantly inhibited the production of OVA-specfic IgE and IgG1. GF-2 not only decreased the release of IL-5 but also increased the production of IL-10 and IFN-γ in splenocytes. Considering these results, we suggested that GF-2 could attenuate IL-5 by enhancing the production of IL-10 and IFN-γ. Furthermore, we evaluated the preventive effect of GF-2 in asthmatic animal model. The results showed that GF-2 decreased airway hyperresponsiveness (AHR), eosinophilia and Th2 cytokines secretion. In conclusion, we suggested that GF-2 could modulate the response of asthma and we hope GF-2 might be used as novel therapeutic reagent for asthma treatment.

目 錄
論文口試委員審定書
授權書
目錄………………………………………………………………..Ⅰ∼Ⅶ
謝誌………………………………………………………………..Ⅲ∼Ⅳ
英文摘要………………………………………………………………..Ⅴ
中文摘要…………………………………………………………..Ⅵ∼Ⅶ
第壹章、 中文摘要研究背景及文獻資料回顧…………………1∼15
第一節、 樟芝生理活性……………………………………….2∼5
第二節、 後天性免疫反應…………………………………….5∼8
第三節、 氣喘………………………………………………...8∼15
第貳章、 研究動機與目的……………………………………..16∼17
第參章、 探討粗萃樟芝多醣體對樹突細胞之影響…………..18∼25
第一節、 實驗目的與原理……………………………………….19
第二節、 實驗材料與方法………………………………….20∼24
第三節、 實驗結果……………………………………………….25
第肆章、 探討GF-2對樹突細胞之影響以及是否可藉由刺激
樹突細胞進而調控CD4+T細胞之分………………26∼35
第一節、 實驗目的與原理……………………………………...27
第二節、 實驗材料與方法………………………………...28∼32
第三節、 實驗結果………………………………………...33∼35
第伍章、 探討GF-2是否可做為免疫佐劑進而影響動物經由OVA所引發之專一性抗原免疫反應……………………..36∼41
第一節、 實驗目的與原理……………………………………...37
第二節、 實驗材料與方法………………………………...38∼40
第三節、 實驗結果……………………………………………...41
第陸章、 探討GF-2在OVA專一性氣喘動物模式中
之治療效果…………………………………………..42∼50
第一節、 實驗目的與原理……………………………………...43
第二節、 實驗材料與方法………………………………...44∼48
第三節、 實驗結果………………………………………...49∼50
第柒章、 討論…………………………………………………..51∼56
第一節、 樟芝多醣體對樹突細胞及T淋巴球之影響…..52∼53
第二節、 樟芝多醣體對氣喘動物模式之影響…………...53∼56
第捌章、 結論與未來方向……………………………………..57∼59
第玖章、 圖表…………………………………………………..60∼89
第壹拾章、參考文獻……………………………………………90∼106

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