公共衛生學院: 職業醫學與工業衛生研究所指導教授: 鄭尊仁程欣源Cheng, Hsin-YuanHsin-YuanCheng2017-03-062018-06-292017-03-062018-06-292015http://ntur.lib.ntu.edu.tw//handle/246246/277380流行病學與毒理學研究皆有發現懸浮微粒不僅對心血管系統有影響，亦可能會對中樞神經系統產生負面的影響。多數的毒理學研究顯示其可能的機制為神經發炎反應進而造成行為改變。在本研究中，我們利用柴油引擎微粒 (DEPs) 探討急性暴露對中樞神經系統的毒性，也利用大氣細懸浮微粒 (PM2.5) 探討亞慢性暴露對中樞神經系統的影響。 本研究分為兩個部分，第一部分，C57BL/6 小鼠以氣管灌注的暴露方式暴露柴油引擎微粒，一周後進行莫式水迷津測試，再分別以學習期的逃脫時間、移動距離、累積相對距離和測試期的區域停留時間、區域經過次數、平均相對距離檢驗小鼠的空間學習與記憶能力。動物犧牲後以H&E染色進行腦組織病理檢驗。第二部分，C57BL/6 小鼠則以呼吸暴露的方式暴露大氣細懸浮微粒12周 (3個月)，暴露完後一周進行莫式水迷津測試，同樣計算小鼠的空間學習與記憶能力。另外，小鼠藉由H&E染色進行腦組織病理檢驗。 第一部分研究結果顯示急性暴露於柴油引擎微粒會使小鼠於莫式水迷津學習期的表現較差，需要較長的逃脫時間與移動距離才能找到平台，累積相對距離也較長。腦組織病理檢驗未在暴露組與控制組間發現顯著差異且在正常範圍內。第二部分研究中，12周大氣細懸浮微粒暴露的平均質量濃度為11.9 μg/ m3。低濃度亞慢性呼吸暴露於大氣細懸浮微粒後，同樣在莫式水迷津學習期中發現其對小鼠的表現有所影響。小鼠的腦組織病理檢驗未在暴露組與控制組間發現顯著差異且在正常範圍內。 過去的研究發現懸浮微粒暴露後的行為變化可能與神經發炎有關，我們發現急性暴露於柴油引擎微粒或低濃度亞慢性呼吸暴露於細懸浮微粒都可以在莫式水迷津的學習期發現小鼠的表現有所變化，未來需要進一步的生化檢驗、腦部發炎細胞染色與組織病理檢驗去探討相關機制並驗證行為實驗的結果。Epidemiological and toxicological studies have shown that particulate matter may not only have adverse effects in the cardiovascular system but also in the central nervous system (CNS). Most toxicological studies suggested that particulate matter may cause neuroinflammation and behavioral changes. Here, we used diesel exhaust particles (DEPs) to explore its acute CNS toxicity and also used ambient fine particles (PM2.5) to discuss sub-chronic exposure induced CNS toxicity. There are two parts in this study. In the first part of study, C57BL/6 mice were given DEPs by intratracheal instillation. One week after exposure, Morris water maze was conducted. Escape latency, distanced moved and cumulative distance from the center of platform quadrant or platform in acquisition phase, percentage of time spent in target area, area crossing and average proximity from the center of platform quadrant or platform were calculated to examine spatial learning and memory. Histopathological examination was then conducted in the brain using H&E stain. In the second part of study, C57BL/6 mice were exposed to ambient PM2.5 by inhalation for 12 weeks (3 months). Morris water maze was then conducted one week after the end of exposure. Spatial learning and memory ability were tested. Histopathological examination was also conducted in the brain using H&E stain. In the first part of study, results in Morris water maze test showed that acute exposure to DEPs may impair performance in acquisition phase. Mice required longer escape latency and distance moved to find the platform. Cumulative distance from the center of platform quadrant or platform was also longer. Mice histopathological examination found no significant difference between exposure and control group and was within normal limit. In the second part of study, the mean mass concentration for exposed ambient PM2.5 was 11.9 μg/ m3 during the exposure duration. Sub-chronic exposure to low concentration ambient PM2.5 may also impair performance in acquisition phase in Morris water maze test. Histopathological examination found no significant difference between exposure and control group and was within normal limit. Previous studies found that behavioral changes after PM exposure may associated with neuroinflammation. We found that both acute exposure to DEPs and low concentration sub-chronic exposure to ambient PM2.5 may affect performance in acquisition phase in Morris water maze test in mice. Further biochemical examination, inflammatory cells staining in the brain and detailed histopathological were required to explore the mechanism and support current findings in behavioral changes.5234770 bytesapplication/pdf論文公開時間: 2017/9/14論文使用權限: 同意無償授權柴油引擎微粒 (DEPs)氣管灌注 (I.T.)大氣細懸浮微粒 (PM2.5)呼吸暴露莫式水迷津空間學習與記憶Diesel exhaust particles (DEPs)Intratracheal instillation (I.T.)ambient fine particles (PM2.5)InhalationMorris water mazeSpatial learning and memorythesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/277380/1/ntu-104-R02841007-1.pdf