2012-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658149摘要：氣喘是兒童最常見的慢性疾病，台灣及許多國家的氣喘盛行率近年來呈現上升的趨勢。流行病學的研究顯示大氣微粒汙染會造成氣喘惡化，也可能會增加氣喘的發生率。由於微粒成分複雜，粒徑小可深入人體呼吸道，可經由直接毒性或氧化壓力造成呼吸道上皮受損，微粒表面也可能吸附過敏原而誘發或加重過敏反應。了解各種粒徑及來源的大氣微粒汙染與氣喘發生及惡化的關係，是公共衛生上的重要課題。國內對於空氣汙染與氣喘的關係大多為流行病學研究，對於微粒暴露後，呼吸道發炎細胞及免疫介質的影響等呼吸毒理研究較為欠缺。因此本研究將以小鼠氣喘模式探討大氣懸浮微粒暴露對小鼠氣喘反應的影響，包括微粒對氣喘惡化的作用以及在氣喘發展過程中，於致敏期暴露微粒是否有加強氣喘發生的作用。第一年計畫除建立氣喘動物模式外，我們也將收集交通污染區、工業污染區及背景區不同粒徑的懸浮微粒，在氣喘模式的誘發期前，給予實驗動物暴露不同來源、不同粒徑大小的懸浮微粒後，測量小鼠的氣道過度反應以及各種免疫細胞及介質，以了解不同微粒對氣喘急性發作的影響。第二年計畫則將聚焦在微粒暴露對氣喘發生的作用，除了將收集的交通污染區、工業污染區及背景區大氣微粒，在氣喘模式的致敏期，給予實驗動物暴露，以探討不同來源、不同粒徑大小的懸浮微粒是否在氣喘發生有加強作用外，也將使用本實驗室開發的微粒暴露系統，探討在致敏期時，於最接近真實微粒暴露環境下，是否會造成氣喘發生的增加。本研究結果將可增進微粒空氣汙染與氣喘惡化及發生相關機轉的了解，結果也可應用於風險評估，對於預防氣喘患者惡化及降低氣喘盛行率將有所助益。<br> Abstract: Asthma is the most common chronic disease in children. The prevalence rate is increasing in many countries, including Taiwan. There are many epidemiological evidences indicate that ambient particulate matter (PM) exposure can cause asthma exacerbation and perhaps exert an adjuvant effect in the development of asthma. PM is the major component of air pollution, which can penetrate into the alveoli of the human’s airway. The components of PM depend on their source. PM can cause airway epithelium damage through the direct toxicity or increased oxidative stress, then adsorb allergens onto their surface, resulting in exacerbation or development of allergic airway inflammation. Given the public health implications of PM exposure in asthma, it is important to elucidate the relationship between different PM exposure and asthma and their underlying mechanism. Since most studies involving particulate matters and asthma were investigated in epidemiological study in Taiwan. The goal of the study is to use asthma animal models to investigate the effect of different PM exposure during the pathogenesis of asthma, regarding the asthma development and progression.In the first year, we are planning to establish an asthma animal model. We will also use the particle sampler to collect ambient particulate matter including PM<10μm, PM<2.5μm, PM<1μm and PM<0.1μm from three different (traffic, industry, and background) pollution areas. The compositions of the collected PM will be analyzed. Animals will be exposed to PM by oropharyngeal aspiration before challenge phase, then airway hyperresponsiveness, serum specific antibodies, inflammatory cells and proinflammatory cytokine in bronchoalveolar lavage fluid will be determined. Lung pathology will also be examined. In the second year, we will examine the adjuvant effect of PM exposure in the development of asthma. Animals will be exposed to PM by oropharyngeal aspiration during the sensitization phase. Further, a group of animals will be exposed to ambient particulate matter during the sensitization phase using an inhalation exposure system to simulate real world exposure. Our study will improve our understanding about the mechanisms of PM exposure in the development and exacerbation of asthma. The results can also be used for risk assessment and regulatory setting.氣喘微粒暴露動物模式Asthmaparticulate matteranimal model