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研究生:陳明志
研究生(外文):Chen Ming-Chih
論文名稱:濃縮空氣微粒對肺高血壓大鼠呼吸道毒性相關之研究
論文名稱(外文):Effects of concentrated ambient particles on airway toxicity in pulmonary hypertensive rats.
指導教授:鄭尊仁鄭尊仁引用關係黃嵩立黃嵩立引用關係
指導教授(外文):Cheng Tsun-JenHuang Song-Lih
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:84
中文關鍵詞:濃縮空氣微粒肺高血壓大鼠肺功能發炎反應彗星試驗氧化壓力
外文關鍵詞:concentrated ambient particlespulmonary hypertensive ratspulmonary function testinflammation markerscomet assayROS
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流行病學研究指出,大氣懸浮微粒暴露會使呼吸道疾病盛行率增加,並與心肺疾病死亡率及肺癌有關。不過目前大氣微粒暴露與其引起的健康危害效應間的生物機轉並不十分清楚,因此本研究利用肺高血壓大鼠動物模式來探討微粒所引發的肺功能改變、 肺部發炎指標及DNA傷害等健康危害效應。
以11隻Sprague-Dawley rats以腹腔注射monocrotaline引發肺高血壓,利用微粒濃縮器於新莊超級測站進行連續三天、每天六小時之濃縮微粒暴露實驗,暴露組為暴露於濃縮微粒(平均數目濃度:2.4x105,質量濃度:371.7g/m3 )下之大鼠,對照組為暴露於過濾空氣下之大鼠,實驗分為呼吸道發炎指標、肺功能指標以及氧化壓力、DNA單股斷裂三部分:
(1)利用非侵入性呼吸生理監測儀(Buxco)於暴露前後測定肺功能,肺功能測試包括以生理食鹽水及methacholine刺激試驗。
(2)暴露48小時後,抽取肺泡灌洗液計數總細胞數及白血球分類,測定總蛋白質濃度和LDH值,並以ELISA測定細胞激素IL-6及TNF-α。
(3)暴露48小時後,測量氧化壓力指標,以肺部組織測量GSH,以ELISA測定血漿中8-OHdG,並以彗星試驗分析周邊血球DNA單股斷裂之情形。
結果顯示暴露於濃縮微粒之肺高血壓大鼠以methacholine(15mg/ml)刺激後,暴露前後呼吸道阻塞指標(Penh)改變量與對照組相比有顯著差異(1.5 + 2.1 vs. -2.4 + 2.2,P<0.05 ),暴露組之總細胞數(187.9 + 32.7 vs. 84.8 + 17.1 x 104cell)、總蛋白質濃度(2.6 + 0.3 vs. 1.6 + 0.2 mg/ml)、IL-6(141.4 + 7.4 vs.129.8 + 4.9 pg/ml )與對照組相比,皆達到顯著差異(P<0.05)。但是周邊血球之DNA單股斷裂及氧化壓力指標兩組並沒有差異。
本研究顯示肺高血壓大鼠暴露於濃縮空氣微粒後,會改變肺功能以及造成呼吸道發炎反應,並推斷吸入濃縮空氣微粒所造成的呼吸道阻塞和中樞神經性的反射反應比較有關,和呼吸道的慢性發炎比較無關。因此本研究有助於釐清微粒所造成的呼吸道毒性效應。

Epidemiological studies have demonstrated the association between particulate matters exposure and cardiopulmonary mortality, but the biological mechanisms remain unknown. Thus, we exposed pulmonary hypertensive rats to concentrated ambient particles, then examined their lung injury and pulmonary function. We also used 8-OHdG and GSH and comet assay to evaluate the oxidative stress and DNA damage.
Eleven pulmonary hypertensive rats were exposed to concentrated ambient PM by nose-only inhalation in Shin-Chuang. The exposure group (n=5) was exposed to concentrated ambient particles 6 hours each day for 3 consecutive days (mean number concentration= 2.4x105, mean mass concentration= 371.7g/m3). Control group (n=6) was exposed to filtered air. Lung function was measured before and after exposure. Rats were sacrificed 48hr after the exposure, then inflammation markers, cytokine (IL-6 and TNF-α) in BAL were analyzed. The ROS marker 8-OHdG and GSH were also analyzed. DNA single strand breakage was determined using comet assay.
Our results revealed that exposure to particulate matters could increase airway resistance. The difference of Penh using methacholine challenge (15mg/ml) measured before and after exposure were significant different between exposure and control group. (1.5 + 2.1 vs. -2.4 + 2.2, P<0.05). Exposure group had a significantly higher total cell numbers (187.9 + 32.7 vs. 84.8 + 17.1 x 104cell), total protein (2.6 + 0.3 vs. 1.6 + 0.2 mg/ml), IL-6 in BAL (141.4 + 7.4 vs. 129.8 + 4.9 pg/ml ) as compared to control group (p<0.05). There was no change in DNA damage and ROS markers after PM exposure.
In summary, our results indicated that concentrated ambient PM could enhance airway responsiveness and increase lung injury in MCT rats. We suggest that particle induced airway hyperresponsiveness is associated with nerves reflex, not with the airway inflammation. These findings shed light on the mechanism of PM toxicity.

摘要 i
Abstract ii
目錄 iii
圖表目錄 iv
第一章 前言 6
第二章 文獻回顧 8
2.1微粒空氣污染之流行病學研究 8
2.2微粒的特性 9
2.3微粒與呼吸道發炎反應 11
2.3.1 肺部損傷及發炎反應 11
2.3.2 體外細胞實驗、人體試驗及動物實驗 .12
2.4微粒與肺功能指標 14
2.4.1 微粒與氣喘及肺功能改變 14
2.4.2 呼吸道過度反應 15
2.4.3 肺功能測定 17
2.5 微粒與氧化壓力及DNA單股斷裂 19
2.5.1 微粒毒性及氧化壓力 19
2.5.2 DNA傷害及潛在致癌性 21
2.5.3 DNA傷害指標:DNA斷裂與彗星分析 22
第三章 材料與方法 24
3.1肺動脈高血壓大鼠動物模式 24
3.2濃縮微粒暴露系統 25
3.3肺功能測量 27
3.4肺高血壓大鼠暴露實驗 28
3.5資料處理與統計分析 29
第四章 實驗結果 30
4.1微粒與肺部損傷及發炎反應 30
4.2微粒與肺功能指標 31
4.3微粒與DNA傷害指標 34
第五章 討論 36
5.1 微粒與呼吸道發炎反應 38
5.2 微粒對肺功能的影響 40
5.3 微粒與氧化壓力及DNA傷害 43
第六章 參考文獻 47

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陳衍政,大氣懸浮微粒之毒性研究:微粒粒徑與成份對A549細胞株釋放細胞激素之影響,台灣大學職業醫學與工業衛生研究所碩士論文,1999.
詹長權等,微粒空氣污染健康風險評估計畫-期末報告EPA-91-FA11-03-91DF02

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