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研究生:徐晨維
研究生(外文):Chen-Wei Hsu
論文名稱:腐食酪蟎第三型過敏原之重組蛋白(rTyrp3)及佐劑(CpG或FIP)對小鼠的過敏性氣喘之減敏作用
論文名稱(外文):Effects of coadministration of the recombinant allergen from Tyrophagus putrescentiae (rTyr p 3) and oligo-deoxynucleotides CpG or FIP on the allergic asthma in mice model.
指導教授:何兆美何兆美引用關係
指導教授(外文):Chau-Mei Ho
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:83
中文關鍵詞:腐食酪蟎過敏性氣喘減敏作用氣道過度反應致敏作用調節性T細胞
外文關鍵詞:Tyrophagus putrescentiaeallergic asthmaimmunotherapyAirway hyperresponsivenesssensitizationTreg
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過敏性氣喘(allergic asthma)為近年來常見的慢性疾病,會因呼吸道黏液分泌過多導致呼吸道阻塞,或因氣道緊縮,甚至導致休克或死亡,此現象為呼吸道過度反應(airway hyper-responsiveness)。本實驗室以腐食酪蟎(Tyrophagus putrescentiae)為過敏原進行致敏,再以腐食酪蟎第三型過敏原之重組蛋白質(rTyr p 3)輔以佐劑進行減敏治療,以探討rTyr p 3在動物實驗模式之減敏機轉,利用腐食酪蟎蛋白質萃取液經由腹腔注射後小鼠血液中之IgE和IgG1均上升,表示已達致敏狀態。減敏劑是實驗室中利用細菌表現出之重組蛋白質rTyr p 3已於,其分子量為27KDa,佐劑是合成之寡核甘酸CpG或由大腸桿菌所表現出的免疫調控蛋白質(FIP),其分子量約13KDa,以鼻腔滴入法治療14天。兩天後由氣道注入粗萃取液,再用肺阻力儀觀察小鼠肺功能以確定氣道之反應。結果顯是以rTyr p 3輔以佐劑CpG或FIP治療之小鼠,其肺功能指數(Penh)有明顯的下降。藉由流式細胞儀觀測小鼠血液細胞中能分泌細胞激素IFN-γ或IL-4兩種T細胞的比例,利用rTyr p 3輔以佐劑治療之小鼠可以檢測出有IFN-γ較多,表示其免疫反應已被導向Th1。在此類小鼠體內有Foxp3之細胞較多且產生細胞激素IL-10,表示Treg細胞被活化,由小鼠肺泡沖洗液(BALF)中細胞計數發現,rTyr p 3輔以佐劑CpG或FIP減敏之小鼠其中發炎細胞有明顯的減少。小鼠肺組織切片亦可發現此組之小鼠其呼吸道柱狀上皮細胞及發炎細胞的浸潤都有明顯的改善,由此可推測rTyr p 3輔以佐劑CpG或FIP進行減敏可活化Treg細胞調控,且有使Th2反應導向Th1之作用。
Allergic asthma appears to be one of the most common chronic diseases in recent year. When allergic patient expose to inhale allergens, like mite or pollen, may develop symptom like asthma. Tyrophagus putrescentiae (Tp) appears to be one of the common allergens in the environment and potentially causes allergic asthma in sensitized individuals. In the present study, we used Balb/c mice as an animal model to study the treatment of allergic asthma caused by Tp. The therapeutic agents contained recombinant protein of group 3 allergen in T. putrescentiae (rTyr p 3), which has molecular weight about 27 KDa and has been identified as major allergen. Oligodeoxynucleotides (CpG-ODNs) and fungal immunomodulatory protein (FIP) with the molecular weight 13 KDa were used as adjuvants. After intraperitoneal (IP) administra-tion of the crude extract of Tp, we found IgE and IgG1 increased in sensitized mice. Sensitized mice also showed airway hypersensitivity responses (AHR) to the intratracheal challenged with the crude extract, Tp. However, after local nasal immunotherapy(LNIT) with rTyr p 3 in conjunction with ODN (CpG) or FIP, the allergen-induced airway hyperreactivity in the sensitized mice was attenuated. The mice had polarized the cytokine balance towards Th1 cytokines, decreased IgE and IgG1, and increased IgG2a in serum. In these hyposensitized mice, there were decreased infiltration of inflammatory cells in lung, reduced eosinophils in BALF. After LNIT, IL-12 were increased and Th2 cytokines, IL-5 and IL-13, were decreased, and proflammatory cytokine, IL-17 and IL-23, were all decreased. The IL-10+ /Foxp3+/CD4+ CD25+ were also increased. These results suggest that combinating rTyr p 3 and CpG, or rTyr p 3 and FIP could upregulate Th1 cells and downregulate Th2 cells and may enhance activation Treg response. These results support that this kind of immunotherapy is an effective strategy for the treatment of allergic asthma.
中文摘要……………………………………………………… 4
英文摘要……………………………………………………… 6
壹、 緒論 …………………………………………………… 8
貳、 材料 …………………………………………………… 17
參、 實驗方法 ……………………………………………… 21
肆、 結果 …………………………………………………… 43
伍、 討論 …………………………………………………… 52
陸、 參考文獻 ……………………………………………… 55
柒、 圖及表 ………………………………………………… 59
捌、 附錄 …………………………………………………… 79
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