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Title: | 利用靈芝蛋白及多醣體進行免疫調節以減緩氣喘之呼吸道發炎反應 Application of Ling Zhi-8 (rLZ-8) and polysaccharide (PS-G) from Ganoderma lucidum as immunomodulators for alleviation of airway inflammation in mite-induced murine model of asthma |
Authors: | Chih-Ling Chang 張芷菱 |
Advisor: | 江伯倫(Bor-Luen Chiang) |
Keyword: | 氣喘,靈芝,多醣體,LZ-8, asthma,polysaccharides,LZ-8,Ganoderma lucidum, |
Publication Year : | 2007 |
Degree: | 碩士 |
Abstract: | 靈芝(Ganoderma Lucidum) 為一種在中國及其他亞洲國家中被廣為使用的古老漢方中藥。Ling Zhi-8 (LZ-8)為從靈芝中純化出的蛋白分子,研究發現其具有免疫調節功能。另外,多醣體(PS-G)為靈芝的另一生物活性物質。目前發現其免疫調節功能包括促進抗原呈現細胞功能、加強單核球細胞吞噬功能、提高體液性免疫力及細胞性免疫力。 氣喘為目前世界上最普遍發生的過敏性疾病,約有數百萬的兒童及成人面臨此種疾病。過敏性氣喘通常伴隨有呼吸到過度反應、嗜酸性白血球在肺部的浸潤、呼吸道黏液分泌過多等症狀。家塵螨Dermatophagoides pteronyssinus 第二群過敏原 (Der p2)為主要過敏原。因此綜合先前的研究,我們期望rLZ-8及PS-G免疫調節功能將可作為治療過敏性疾病的一個方法。此研究中,我們給予樹突細胞rLZ-8及PS-G刺激,發現rLZ-8及PS-G可以增加IL-12p40之產生,並且促進樹突細胞成熟表現CD86, CD83, and MHC Ⅱ分子。此外rLZ-8及PS-G刺激後的樹突細胞與T細胞共同培養,可以增加T細胞增生能力及產生IFN-γ及IL-4。在中和反應實驗中發現,給予TLR-4抗體可以明顯抑制樹突細胞分泌IL-12p40,顯示IL-12p40的訊息傳導是經由TLR-4路徑。更進一步地,我們利用家塵螨誘導小鼠氣喘模式來研究rLZ-8及PS-G的免疫調節能力。實驗一,小鼠致敏後連續鼻腔給予rLZ-8及PS-G研究其治療效果。實驗二,致敏時混合抗原與rLZ-8或PS-G同時給予小鼠研究其預防效果,小鼠犧牲後同樣分析呼吸道阻力、肺功能、第一型輔助型T細胞激素及第二型輔助型T細胞激素及rDer p2專一性抗體。我們的研究發現,rLZ-8及PS-G在體外實驗確實可以促進樹突細胞的成熟與活化,顯示這兩個分子具有免疫調節能力。動物實驗結果顯示,rLZ-8及PS-G可抑制呼吸道阻力產生及血清的IgE。PS-G可減少肺沖洗液及胰臟細胞IL-4和IL-5之產生,而rLZ-8可減少肺沖洗液IL-5產生。因此rLZ-8及PS-G可改善氣喘的徵狀,但其作用機制則需要更進一步地釐清。 Ganoderma Lucidum, a China herb, has been widely used in China and other Asian countries. G. Lucidum has been reported to be effective in modulating immune functions. Ling Zhi-8 (LZ-8) is a protein derived from the fungus Ganoderma lucidum and the polysaccharide from Ganoderma Lucidum (PS-G) is a branched (1 → 6)-β-D-glucan moiety. Asthma is one of the most prevalent chronic airway inflammatory diseases in the world. The house dust mite, Dermatophagoides pteronyssinus (Der p), is the major allergen, and is the dominant species collected in Taiwan. Therefore, we like to investigate whether rLZ-8 and PS-G might exert a regulatory role in the treatment of allergic diseases. In this study, we first investigated the immunomodulatory effects of rLZ-8 and PS-G on BMDCs. The result showed that rLZ-8 and PS-G enhanced the expression of cell surface markers including CD86, CD83, and MHC Ⅱ, as well as the enhanced production of IL-12 p40 and IL-10. In addition, rLZ-8 or PS-G-treated BMDCs could promote T cell proliferation capacity, and increased T cell secretion of IFN-y. In animal Experiment Ⅰ, immunized female BALB/c mice were consistently intranasally received rLZ-8 and PS-G for treatment. In Experiment Ⅱ, mice were immunized (i.p.) injection of rDer p2 admixed with rLZ-8 or PS-G for investigating the preventive effect. Further, airway hyperresponsiveness, pulmonary function, TH1/TH2 cytokine production, and immunoglobulin levels will be followed. In conclusion, we demonstrated that rLZ-8 and PS-G effectively promoted the activation and maturation of immature BMDCs, suggesting that rLZ-8 and PS-G may possess a potential effect in regulating immune responses. In vivo result showed that both rLZ-8 and PS-G reduced airway hyperresponsiveness and serum IgE level. Moreover, PS-G could decrease the level of IL-4, IL-5 in BALF and splenocyte. rLZ-8 reduced IL-5 level in BALF. Although rLZ-8 and PS-G could modulate the response of asthma, the effect of these two molecules should be clarified in the future. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28094 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 口腔生物科學研究所 |
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