臺灣博碩士論文加值系統

背景介紹
台灣是一個四面環海的亞熱帶島嶼國家，常年濕熱的天氣是塵蟎生長的最佳條件。家塵蟎 (HDM) 是亞熱帶地區常見的引起過敏疾病甚至是氣喘的過敏原。台灣有 3 種本地品種的 HDM，包括微角塵蟎 (Der m)、蕨類蟎 (Der p)以及粉塵蟎 (Der f)。從以往的研究來看，台灣中部地區80%以上的兒童接觸了Der m過敏原後的過敏致敏率。
益生菌已被證明具有改變免疫系統和改變過敏性氣道疾病進程的能力。我們之前的研究表明，口服鼠李糖乳桿菌 GG (LGG) 可以改善氣道發炎和氣道重塑。此外，益生菌的給藥途徑是影響其功效的最重要因素之一。而目前大多數評估益生菌效果的研究仍是以口服給藥途徑，而較少評估鼻腔給藥的方式。
本研究透過探討HDMs (Der m2) 過敏原的致敏性，並比較益生菌 LGG 在鼻噴霧和口服給藥中的效果。
材料與方法
本研究使用雌性、BALB/c小鼠並使用Der m2作為致敏氣喘模型的過敏原。於實驗進程的第1、2和3天以腹腔注射Der m2使小鼠第一階段接觸過敏原，第14、17、21、24和27天以鼻腔滴定Der m2作為再次遇到過敏原後的激發作用。前期給藥組為在第 1 天至第 14 天通過鼻噴霧或口服給與LGG，為後期給藥組則在第 14 至第 27 天中使用 LGG 治療。我們還評估了 使用鼻噴給藥與口服給予LGG 在呼吸道阻力、血清特異性 IgE/IgG2a、肺部細胞浸潤狀況和 BALF 中的細胞激素等表現上的差異與影響。
結果
與Der m2致敏組相比，LGG經鼻噴霧或口服給藥組均能抑制過敏氣喘症狀，如AHR、過敏原特異性IgE、Th2細胞因子減少和發炎細胞浸潤等。此外，益生菌 LGG 在鼻腔噴霧中的療效優於口服給藥的方式。
結論
LGG可改善Der m2致敏小鼠，有利於氣喘的治療。 LGG鼻噴霧劑的療效可能優於口服給藥。

Introduction
Taiwan is a subtropical island surrounded by the oceans, and the perennial hot and humid weathers are the best conditions for house dust mites to grow. House dust mites (HDMs) are commonly known allergens to cause asthma in the subtropical area. There are three local breed HDMs in Taiwan including Dermatophagoides microceras (Der m), Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinaea (Der f). From the previous studies, more than 80% allergies sensitization rate exposure by the Der M allergens for children in the central Taiwan.
Probiotics have been shown the ability to modify the immune system and alter the course of allergic airway disease. Our previous studies showed that oral Lactobacillus rhamnosus GG (LGG) could improve airway inflammation and airway remodeling.
The route of probiotic administration is one of the most important factors affecting its efficacy. Until now, most studies evaluating the effect of probiotics have paid attention to the oral administration route, while the nasal administration route has less been considered.
Explore the sensitization of HDMs (Der m2) allergens and compare the efficacy of probiotic LGG in nasal spray and oral administration.
Material and methods
We used Der m2-sensitized asthma model in female BALB/c mice with intraperitoneal Der m2 sensitization on day 1, 2 and 3, and intranasal Der m2 challenge on day 14, 17, 21, 24 and 27. The animals were treated with LGG by nasal spray or oral administration in pre group during on day 1to 14 or in post group during on day 14 to 27. We also assessed the LGG appears in the airway hyperresponsiveness, serum specific-IgE/ IgG2a, infiltrating inflammatory cells in lung and cytokines in BALF.
Results
Compared to Der m2 sensitization group, per- and post- LGG nasal spray or oral administration groups were suppressing asthma symptoms such as AHR, allergen specific-IgE, decrease Th2 cytokines and infiltrating inflammatory cells. Moreover, the efficacy of probiotic LGG in nasal spray was better than oral administration.
Conclusions
LGG may improve in Der m2 sensitization mice could be beneficial in the treatment of asthma. The efficacy of LGG by nasal spray may better than oral administration.

目錄
謝 誌 ………………………………………………………I
中文摘要 …………………………………………………III
英文摘要 …………………………………………………V
第一章 前言
1.1 研究背景與動機 …………………………………………………1
1.2 研究目的 …………………………………………………………3
第二章 文獻探討
2.1 過敏 ………………………………………………………………４
2.2 常見的過敏疾病 …………………………………………………7
2.2.1 氣喘 …………………………………………………………7
2.2.2 過敏性鼻炎 ………………………………………………10
2.2.3 異位性皮膚炎 ……………………………………………11
2.3 過敏性疾病流行現況 ……………………………………………12
2.4 益生菌 ……………………………………………………………13
2.5 塵蟎(House dust mite, HDM) ……………………………………15
2.6常見的鼻噴劑用藥 ………………………………………………17
第三章 材料與方法
3.1 實驗動物 …………………………………………………………19
3.2 益生菌的備製 ……………………………………………………19
3.3 微角塵蟎蛋白純化 ………………………………………………20
3.4 重組純化之Der m2內生性LPS定量 …………………………21
3.5 實驗分組 …………………………………………………………21
3.6 動物實驗模式 ……………………………………………………21
3.7施藥時間與劑量 …………………………………………………22
3.8 動物實驗檢測……………………………………………………23
3.9 統計分析 …………………………………………………………25
第四章 結果
4.1以鼻腔滴定/口服益生菌LGG對於Der m2致敏鼠在呼吸道過度
反應上的影響……………………………………………………26
4.2以鼻腔滴定/口服益生菌LGG對於Der m2致敏鼠對血清中特異
性過敏原球蛋白的影響………………………………………26
4.3 以鼻腔滴定/口服益生菌LGG對於Der m2致敏鼠對細胞浸潤的
影響………………………………………………………………26
4.4以鼻腔滴定/口服益生菌LGG對於Der m2致敏鼠對肺泡沖洗液
中各種細胞激素的影響 …………………………………………27
4.5 以鼻腔滴定/口服益生菌LGG對於Der m2致敏鼠對呼吸道發炎
現象的影響 ………………………………………………………28
第五章 討論 ………………………………………………………29
參考文獻 ……………………………………………………………32
圖表說明……………………………………………………………39

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