奈米銀微粒對氣喘模式小鼠之呼吸毒理研究

Inhalation Toxicity of Silver Nanoparticles in a Murine Model of Allergic Asthma

胡靜君(Cheng-Kuan Wu)

指導教授 ： 鄭尊仁

共同指導教授 ： 王根樹

國立臺灣大學/公共衛生學院/環境衛生研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.03078

摘要

由於全球各地的氣喘盛行率逐年持續上升，加上近年奈米科技產品日新月異，尤其以具有抗菌功效的奈米銀應用至為廣泛，因此大量勞工可能在生產過程中吸入空氣中的奈米銀微粒；除了關注奈米銀對一般健康勞工的呼吸毒性外，針對氣喘此易感族群的相關呼吸毒理研究也有其重要性。
　　本研究利用蒸氣冷凝法產生奈米銀微粒，以進行氣喘動物之呼吸暴露實驗。一開始要先建立氣喘動物模式，將BALB/c小鼠分為健康(PBS)和氣喘模式(OVA)兩組，再細分為奈米銀暴露組(NP)和過濾空氣控制組(FA)。因此四組分別表示為PBS/FA (N=5)、PBS/NP (N=6)、OVA/FA (N=5)、OVA/NP (N=5)，暴露時間為6小時/天，連續7天，結束後測量各組呼吸道阻力。最後分析氣喘疾病及肺部發炎指標，以及肺部病理組織切片。
奈米銀暴露組所暴露之奈米微粒平均粒徑為32.78nm，質量濃度為3.34 mg/m3，經過連續7天的暴露後，可觀察到在健康組間，分別在肺泡灌洗液 (BALF)的嗜酸性白血球比率、嗜中性白血球比率及總死亡細胞數三個生理指標中，PBS/NP相比PBS/FA皆有上升趨勢；而在氣喘組間，則在血清的免疫球蛋白E(IgE)(呼吸暴露後)、BALF的介白素13 (IL-13)和總死亡細胞數(total cell)，以及呼吸道阻力(AHR)這些生理指標中，OVA/NP 相比OVA/FA皆有上升趨勢。而且肺部病理組織切片的結果也顯示，無論是健康組還是氣喘組，經過奈米銀暴露後的發炎反應會較強烈。
目前針對氣喘疾病的奈米銀呼吸毒理研究非常缺乏，本研究使用由奈米微粒產生器所產生之奈米銀氣膠進行呼吸暴露，可觀察到奈米銀對健康或氣喘小鼠皆有不良健康效應之趨勢，惟此趨勢在統計上並不顯著，推估是由於此氣喘模式中致敏劑劑量過高所致，建議應下調劑量以適用於奈米呼吸暴露研究；此外，過去亦有研究顯示奈米銀微粒對氣喘小鼠反而有抑制發炎的作用，因此目前奈米銀微粒對於氣喘模式小鼠的健康效應未有一致結論，其毒理影響及作用機轉仍有待更多相關研究。

關鍵字

奈米銀微粒 ； 氣喘 ； 蒸發冷凝法 ； 呼吸暴露

並列摘要

Nowadays, asthma is one of the most common airway inflammatory disease and its prevalence is high in developed and developing countries. A wide range of silver nanoparticle applications has emerged in consumer products ranging from disinfecting medical devices to water treatment. We are interested in the inhalation toxicity of silver nanoparticles in susceptible allergic asthmatic mice.
In this study, silver nanoparticles were produced in a generation system. The BALB/c mice were divided into normal group (PBS) and asthmatic group (induced by OVA injection). These two groups were further exposed for filtered air (FA) (PBS/FA (N=5)、OVA/FA (N=5)) and silver nanoparticles (NP) (PBS/NP (N=6)、OVA/NP (N=5)) 6 hours a day for one week.
The average size and concentration of NP during exposure was 32.78 nm at 3.34 mg/m3. The inflammation and asthma markers including IgE in serum, IL-13, total protein, total cells, proportion of neutrophils, macrophages and eosinophils in bronchoalveolar lavage fluid (BALF) and AHR (airway hyperresponsiveness) were determined.
The results showed that animals had adverse health effects after exposure to AgNPs (silver nanoparticles). In normal group, percentage of neutrophils, eosinophils and total cells in BALF increased after AgNPs exposure as compared to FA control. In asthma group, IgE, IL-13, AHR and total cells also increased after AgNPs exposure as compared to FA control but it was not statistically significant. These results suggested that asthmatic model needs further modification. Additionally, some previous experiments showed that AgNPs might act as anti-inflammatory agents. Thus，further studies are needed to assess the toxicity of AgNPs in allergic asthma model.

並列關鍵字

silver nanoparticles ； asthma ； evaporation-condensation ； inhalation exposure

參考文獻

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