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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘子明(Tzu-Ming Pan) | |
| dc.contributor.author | Yu-Ying Chang | en |
| dc.contributor.author | 張郁瑩 | zh_TW |
| dc.date.accessioned | 2021-06-16T02:41:56Z | - |
| dc.date.available | 2025-12-31 | |
| dc.date.copyright | 2015-07-23 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-07-21 | |
| dc.identifier.citation | Abdel-Raheem, I. T., Hide, I., Yanase, Y., Shigemoto-Mogami, Y., Sakai, N., Shirai, Y., Saito, N., Hamada, F. M., El-Mahdy, N. A., El-Mahdy, N. A., Sokar, S. S., Nakata, Y. 2005. Protein kinase C-alpha mediates TNF release process in RBL-2H3 mast cells. Br. J. Pharmacol. 145: 415-423.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54146 | - |
| dc.description.abstract | 第一型過敏反應 (type I allergy) 包含氣喘、食物過敏、蕁麻疹等疾病，其盛行率隨著生活方式都市化與現代化而逐漸增加，當人體接觸到過敏原，經由抗原呈現細胞 (antigen presenting cells, APCs) 之辨認、吞噬並呈現給 T 細胞，使得 T 細胞活化及分化，在過敏患者體內 T 細胞趨向分化為 T helper 2 (Th2) 細胞，釋放之 Th2 細胞激素 (cytokines) 包含 interleukin-4 (IL-4)、IL-5、IL-13 等，造成 B 細胞進行型態轉換 (class switching) 而分泌具過敏原專一性之 IgE 抗體，而 IgE 抗體會和肥大細胞表面之 IgE receptor 結合，當過敏病患再次接觸到同一過敏原時，肥大細胞表面的 IgE 會和過敏原形成交互結合 (crosslinking)，導致肥大細胞活化釋放多種發炎介質，使病患發生氣管窄縮、腹瀉、皮膚紅腫等症狀。而先前研究發現，雞卵蛋白 (ovalbuminn) 誘導 BALB/c 鼠呼吸道發炎以模擬氣喘，給予紅麴二次代謝產物monascin 與 ankaflavin 能夠減緩其發炎情形，顯示其具有改善氣喘之潛力，深入研究 monascin 與 ankaflavin 對於參與其中之細胞的影響，發現 monascin 可影響抗原呈現細胞中的樹突細胞之成熟，而可能影響其呈現抗原給 T 細胞，monascin 也可抑制 T 細胞分泌 Th2 細胞激素，但 ankaflavin 對於 T 細胞之影響以及 monascin 和 ankaflavin 對下游之肥大細胞之影響還未被研究，因此期望透過研究這兩種細胞以了解 monascin 及 ankaflavin 對於改善氣喘之可能途徑。實驗結果發現，ankaflavin 能夠抑制經 phorbol 12-myristate 13-acetate (PMA) 及 ionomycin 誘導之 EL4 T 細胞分泌 Th1 與 Th2 細胞激素而具有減緩發炎之潛力，試驗發現 40 μM monascin 與 ankaflavin 對肥大細胞株 RBL-2H3 細胞可以顯著地抑制 PMA 及 ionomycin 誘導之肥大細胞分泌發炎介質組織胺 (histamine) 和腫瘤壞死因子 (tumor necrosis factorα, TNF-α)，因此進一步往上游探討可能的改善機制，結果顯示 monascin 與 ankaflavin 對於細胞內鈣離子與活性氧分子 (reactive oxygen species, ROS) 之產生無影響，但monascin 及 ankaflavin 可藉由抑制 protein kinase C (PKC) 與 mitogen-activated protein kinase (MAPK) family 中之 ERK、p38 及 JNK 蛋白之磷酸化，進而影響肥大細胞釋放 TNF-α 與組織胺等發炎介質。由以上結果得知，紅麴代謝產物 monascin 和 ankaflavin 具減緩 T 細胞分泌 Th1、Th2 細胞激素與調節肥大細胞釋放發炎介質之效果，藉由改善細胞分泌發炎介質而改善病人過敏與發炎之情形，對於第一型過敏反應具改善功效潛力。 | zh_TW |
| dc.description.abstract | Type I allergy includes asthma, food allergy, urticaria and so on. Its prevalence increases with industrialized and modernized lifestyles. The mechanism of type I allergy began with antigen presenting cells (APCs) contacting with allergens, and then APCs recognize, engulfe, and present antigen to naive T cells, which make T cells activated and differentiated. In allergic patients, T cells tended to differentiate into T helper 2 (Th2) cells. Th2 released cytokines included interleukin-4 (IL-4), IL-5, and IL-13 that turn B cells into IgE-releasing plasma cells. The produced IgE bound to IgE receptors on mast cells. As a result, when next time allergy patients contact the same allergen, allergen would cross-link with IgE which is previously bound on mast cells, followed with the activation and inflammatory mediator-secretion of mast cells. These turned out making patients bronchial constriction, diarrhea, and wheal-and-flare reaction. In previous study, treating with Monascus secondary metabolites monascin and ankaflavin to ovalbumin-induced BALB/c mice could ameliorate allergic airway inflammation. It is showed that monascin and ankaflavin may have the anti-asthma potential. In order to know the improving mechanism of monascin and ankaflavin related to which immune cells, our lab investigated the influence of monascin on the APCs dendritic cells and EL4 T cells. We discovered that monascin inhibited the maturation of dendritic cells and reduced the Th2 cytokines release of EL4 T cell. However, the effects of ankaflavin on EL4 T cell and both monascin and ankaflavin on mast cells haven’t been investigated. Therefore, we hope to understand the impact of monascin and ankaflavin on these two cells. According to the results, we found that ankaflavin could reduce the production of PMA/ionomycin-induced Th1 and Th2 cytokine, and may possess anti-inflammatory potential. In RBL-2H3 mast cells, both monasin and ankaflavin (40 μM) decrease PMA/ionomycin-induced mast cell tumor necrosis factor α (TNF-α) release and degranulation. As we further examined the possible mechanism, the results showed that monascin and ankaflavin had no influence over intracellular calcium and reactive oxygen species (ROS) level. Nonetheless, monascin and ankaflvin could improve mast cell activation by controlling the activation and phosphorylation of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) family ERK, JNK, and p38. To sum up, monascin and ankaflavin had regulating effects on the generation of T cell cytokines and mast cell inflammatory mediators. Both may own the potential to improve type I allergy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T02:41:56Z (GMT). No. of bitstreams: 1 ntu-104-R01b22002-1.pdf: 1928790 bytes, checksum: 87981b4af9e8ea35a9b3a1884c6b3ccc (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 縮寫表………………………………………………………………………………………………………………………… II
中文摘要…………………………………………………………………………………………………………………… IV 英文摘要…………………………………………………………………………………………………………………… VI 目錄……………………………………………………………………………………………………………………………… VIII 圖目錄………………………………………………………………………………………………………………………… XI 第壹章 文獻回顧…………………………………………………………………………………………………… 1 ㄧ、過敏反應…………………………………………………………………………… ……………………………… 1 (一) 過敏反應……………………………………………………………………………………………………… 1 1. 盛行率……………………………………………………………………………………………………… 1 (二) 第一型過敏反應之致病機轉………………………………………………………………… 1 1. T 細胞與過敏反應……………………………………………………………………………… 3 2. 肥大細胞與過敏反應………………………………………………………………………… 5 3. IgE 調控肥大細胞活化之訊息傳遞路徑…………………………………… 6 (三) 治療方式………………………………………………………………………………………………………… 9 1. 腎上腺素…………………………………………………………………………………………………… 9 2. 類固醇………………………………………………………………………………………………………… 9 3. 抗組織胺…………………………………………………………………………………………………… 10 4. 減免療法…………………………………………………………………………………………………… 10 5. Cromolyn sodium……………………………………………………………………………… 10 二、紅麴菌…………………………………………………………………………………………………………………… 11 (ㄧ) 紅麴菌……………………………………………………………………………………………………………… 11 (二) 紅麴二次代謝產物 (monascin 與 ankaflavin)…………………… 11 (三) 預防醫學之應用…………………………………………………………………………………………… 12 1. 降膽固醇作用…………………………………………………………………………………………… 12 2. 降體脂作用………………………………………………………………………………………………… 12 3. 降血壓………………………………………………………………………………………………………… 13 4. 抑制腫瘤之作用……………………………………………………………………………………… 13 5. 調節血糖作用…………………………………………………………………………………………… 15 6. 免疫調節……………………………………………………………………………………………………… 16 7. 改善骨質疏鬆…………………………………………………………………………………………… 16 8. 護肝……………………………………………………………………………………………………………… 16 9. 抗疲勞作用………………………………………………………………………………………………… 18 10.改善阿茲海默症……………………………………………………………………………………… 18 三、過氧化體增生劑活化接受器γ (PPARγ)………………………………………………… 18 (一) PPARγ 特性……………………………………………………………………………………………………… 18 (二) PPARγ與過敏及發炎反應之關係……………………………………………………………… 19 1. PPARγ 與 T 細胞………………………………………………………………………………… 21 2. PPARγ 與肥大細胞………………………………………………………………………………… 21 3. PPARγ 與紅麴代謝產物 monascin 與 ankaflavin………… 23 第貳章 研究動機與目的………………………………………………………………………………………… 24 第參章 材料與方法…………………………………………………………………………………………………… 27 ㄧ、藥品試劑…………………………………………………………………………… …………………………………… 27 二、儀器設備…………………………………………………………………………… …………………………………… 28 三、試驗方法…………………………………………………………………………… …………………………………… 28 第肆章 結果與討論…………………………………………………………………………………………………… 33 一、Ankaflavin 抑制 T 細胞分泌細胞激素……………………………………………… 33 二、Monascin 與 ankaflavin 對肥大細胞之影響………………………………… 36 (一) Monascin 及 ankaflavin 對於肥大細胞存活率之影響………… 36 (二) Monascin 及 ankaflavin 抑制肥大細胞之活化………………………… 36 (三) Monascin 及 ankaflavin 改善肥大細胞活化方式並非透過 PPARγ 之相關路徑………………………………………………………………………………………… 38 (四) Monascin 及 ankaflavin 抑制 MAPK 家族之活化………………… 43 (五) Monascin 及 ankaflavin 抑制 protein kinase C 之活化45 (六) Monascin及 ankaflavin 並非透過改善細胞內鈣離子濃度與 活性氧分子之方式達到減緩肥大細胞之效果之影響……………………… 48 第伍章 結論…………………………………………………………………………………………………………………… 52 第陸章 參考文獻………………………………………………………………………………………………………… 54 | |
| dc.language.iso | zh-TW | |
| dc.subject | 過敏 | zh_TW |
| dc.subject | monascin | zh_TW |
| dc.subject | ankaflavin | zh_TW |
| dc.subject | 肥大細胞 | zh_TW |
| dc.subject | T 細胞 | zh_TW |
| dc.subject | monascin | zh_TW |
| dc.subject | ankaflavin | zh_TW |
| dc.subject | 肥大細胞 | zh_TW |
| dc.subject | T 細胞 | zh_TW |
| dc.subject | 過敏 | zh_TW |
| dc.subject | monascin | en |
| dc.subject | monascin | en |
| dc.subject | ankaflavin | en |
| dc.subject | mast cells | en |
| dc.subject | T cells | en |
| dc.subject | allergy | en |
| dc.subject | ankaflavin | en |
| dc.subject | mast cells | en |
| dc.subject | T cells | en |
| dc.subject | allergy | en |
| dc.title | 紅麴代謝產物 monascin 與 ankaflavin 對於過敏反應中肥大細胞與 T 細胞之影響 | zh_TW |
| dc.title | The effect of Monascus metabolites monascin and ankaflavin on mast cells and T cells in allergy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳明汝(Ming-Ju Chen),謝淑貞(Shu-Chen Hsieh),蔣慎思(Shen-Shih Chiang),蔡宗佑(Tsung-Yu Tsai) | |
| dc.subject.keyword | monascin,ankaflavin,肥大細胞,T 細胞,過敏, | zh_TW |
| dc.subject.keyword | monascin,ankaflavin,mast cells,T cells,allergy, | en |
| dc.relation.page | 64 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-07-21 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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