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研究生:張瑋玲
研究生(外文):Wei-Ling Chang
論文名稱:堆高機及汽車柴油引擎微粒心血管毒性之比較
論文名稱(外文):Cardiovascular toxicity study of forklift and automobile diesel exhaust particles in spontaneously hypertensive rats
指導教授:鄭尊仁鄭尊仁引用關係
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:2005
畢業學年度:93
語文別:中文
論文頁數:84
中文關鍵詞:微粒空氣污染柴油引擎微粒超細粒徑碳黑心跳速率變異性心血管疾病自發性高血壓大鼠
外文關鍵詞:particulate air pollutiondiesel exhaust particlesultrafine carbon blackheart rate variabilitycardiovascular diseasespontaneously hypertensive rats
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柴油引擎微粒(Diesel exhaust particles, DEPs)是移動交通污染源中主要污染物之一,研究指出柴油引擎微粒的暴露與呼吸道疾病及肺癌的發生有關同時也可能會影響心血管系統。然而,柴油引擎微粒組成相當複雜,微粒毒性會隨其物理化學特性而改變,任何影響柴油引擎微粒特性的因子如引擎特性、燃油成份等都可能影響微粒毒性,因此本研究即針對堆高機柴油引擎微粒(forklift-derived DEPs, SRM 2975)及柴油車柴油引擎微粒(automobile-derived DEPs, A-DEP)兩種不同來源的柴油引擎微粒進行心血管系統的毒理試驗,比較兩種柴油引擎微粒對心血管生理參數的影響。此外,為了進一步瞭解柴油引擎微粒成分與心血管生理參數的關係,本研究另以超細粒徑碳黑(ultrafine carbon black)代表柴油引擎微粒中超細微粒部分,探討超細粒徑碳黑對自發性高血壓大鼠心跳及心跳變異性的影響,並以不同粒徑之碳黑來瞭解微粒粒徑在心血管生理參數上的效應。
13-15週齡及20-22週齡之自發性高血壓大鼠植入生理循環監測器後,於不同時間以氣管灌注方式暴露生理食鹽水、SRM 2975(500 μg/animal)或A-DEP(500 μg/animal),分析暴露後心跳及心跳變異性變化情形。SRM 2975暴露後,實驗動物有心跳速率降低的情形,反之,A-DEP暴露則會加心跳速率;心跳變異性方面,實驗動物在暴露SRM 2975後心跳變異性明顯增加,而A-DEP暴露則會造成心跳變異性的降低。
超細粒徑碳黑實驗部分,以氣管灌注方式於不同時間點分別給予已植入生理循環監視器之自發性高血壓大鼠生理食鹽水及碳黑(分別為500、1000 μg 14nm碳黑或1000 μg 95nm碳黑),分析暴露後心跳及心跳變異性變化情形。實驗結果顯示14nm碳黑會使老鼠心跳速率上升,心跳變異性增加,但只有在心跳速率變化上有明顯的劑量反應關係;而95nm碳黑暴露會降低老鼠心跳速率,增加心跳變異性。
本研究結果顯示柴油引擎微粒暴露會引起自發性高血壓大鼠心跳速率及心跳速率變異性的變化,可能與自主神經系統異常有關。堆高機與柴油車柴油引擎微粒的暴露均會影響心血管功能,但兩種柴油引擎微粒卻是引起反向的心血管生理參數變化,推測可能與不同柴油引擎微粒的特性有關。由於柴油引擎微粒組成複雜,本研究進一步探討微粒毒性危險因子之一超細粒徑微粒可能扮演的角色,發現並無定論,未來需要進一步的研究來釐清柴油引擎微粒特性與心血管生理參數變化的關係。
Diesel exhaust particles (DEPs), a major contributor of ambient particulate matter, have been reported to be associated with cardiopulmonary diseases and lung cancer. DEPs toxicity, as we know, varies with the complicated physical and chemical properties of particles which are influenced by the engine type, fuel components, sampling procedures, etc, and it is possible that different samples of DEPs may have different toxicity. Therefore, the objective of this study was to compare the effects of two different DEPs samples, forklift-derived DEPs (SRM 2975) and automobile-derived DEPs (A-DEP), on heart rate and heart rate variability (HRV) in spontaneously hypertensive rats (SHR). In order to further investigate the contributions of DEPs components on cardiovascular toxicity, the artifical carbon black (CB) as a surrogate of ultrafine fraction of DEPs is subsequently used to examine the effects of ultrafine particles and particle size on heart rate and HRV in SHR.
13-15 and 20-22 weeks old SHR with implanted radiotelemetry devices were intratracheally administered with both normal saline and SRM 2975 (500 μg/animal, n=3) or (A-DEP 500 μg/animal, n=3) alternatively, so each rat could serve as its own control. ECG signals were recorded for 72 hours after each exposure, and heart rate and parameters of HRV including standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences of adjacent normal-to-normal intervals (RMSSD) were analyzed. Significantly decreased heart rate was observed in SHR following SRM 2975 exposure, whereas increased heart rate was found after A-DEP exposure. HRV (SDNN and RMSSD) were increased after SRM 2975 exposure, whereas SDNN and RMSSD were decreased after A-DEP exposure.
SHR with implanted radiotelemetry devices were intratracheally administered with both normal saline and CB (500 or 1000 μg 14 nm CB, or 1000 μg 95 nm CB; n=4 for each 14 nm CB group, and n=3 for 95nm CB). ECG signals collection and analysis were as previously described. After 14nm CB exposure, increased heart rate and HRV (SDNN and RMSSD) were observed in SHR. However, the dose-response relationship was only found in heart rate change. In addition, a decrement of heart rate and an increase of HRV were observed in SHR following 95nm CB exposure.
Our results showed that DEPs may cause autonomic nervous system dysfunction in SHR. Both SRM 2975 and A-DEP samples can alter cardiovascular function, but the directions of the effects are different. These disparities on heart rate and HRV changes may due to the characteristics of these particles. We further tested the effects of ultrafine particles, one of the risk factors of particle toxicity, without conclusion. Thus, more studies are needed to investigate the specific components of DEPs which may explain the discrepancy of above findings.
摘要 i
Abstract iii
目錄 v
圖目錄 vi
Abbreviations vii
第一章 前言 8
第二章 文獻探討 11
2-1 流行病學研究 11
2-2 空氣懸浮微粒之肺部毒性 12
2-3 空氣懸浮微粒心血管毒性 12
2-4 柴油引擎微粒特性 21
2-5 柴油引擎微粒與心血管系統效應 21
2-6 堆高機柴油引擎微粒(SRM 2975)及汽車柴油引擎微粒(A-DEP) 22
2-7 微粒毒性研究相關疾病動物模式 23
2-7 心跳速率(heart rate)與心跳速率變異性(heart rate variability, HRV) 24
第三章 材料與方法 26
3-1 高血壓大鼠動物模式 26
3-2 堆高機柴油引擎微粒(SRM 2975)及汽車柴油引擎微粒(A-DEP) 26
3-3 動物飼養及循環生理監視器植入與訊號收集 27
3-4堆高機及汽車柴油引擎微粒(SRM 2975及A-DEP)暴露與心血管生理參數 28
3-4-1二十至二十二週齡之SHR暴露實驗 28
3-4-2十三至十五週齡之SHR暴露實驗 29
3-5 超細粒徑碳黑(ultrafine carbon black)與心血管生理參數 30
3-6資料處理及統計分析 31
第四章 實驗結果 33
4-1 SRM 2975及A-DEP暴露與心血管生理參數 33
4-1-1 二十至二十二週齡之SHR暴露實驗 33
4-1-2 十三至十五週齡之SHR暴露實驗 34
4-2 超細粒徑碳黑(ultrafine carbon black)與心血管生理參數 36
第五章 討論 39
5-1 柴油引擎微粒與心血管生理參數 40
5-2 超細粒徑碳黑與心血管生理參數 41
5-3 堆高機及汽車柴油引擎微粒對心血管生理參數的作用 43
參考文獻 47


圖目錄
圖 4-1-1二十至二十二週齡之SHR暴露 SRM 2975後心跳變化 60
圖 4-1-2 二十至二十二週齡之SHR 暴露SRM 2975後adjusted SDNN變化 61
圖 4-1-3 二十至二十二週齡之SHR暴露SRM 2975後RMSSD變化 62
圖 4-1-4 二十至二十二週齡之SHR暴露A-DEP後心跳速率變化 63
圖 4-1-5 二十至二十二週齡之SHR暴露A-DEP後adjusted SDNN變化 64
圖 4-1-6 二十至二十二週齡之SHR暴露A-DEP後adjusted SDNN變化 65
圖 4-1-7 SRM 2975及A-DEP對二十至二十二週齡SHR心跳速率之影響 66
圖 4-1-8 SRM 2975及A-DEP對二十至二十二週齡SHR adjusted SDNN之影響 66
圖 4-1-9 SRM 2975及A-DEP對二十至二十二週齡SHR RMSSD之影響 67
圖 4-1-10 十三至十五週齡之SHR暴露SRM 2975後心跳變化 68
圖 4-1-11 十三至十五週齡之SHR暴露SRM 2975後adjusted SDNN變化 69
圖 4-1-12 十三至十五週齡之SHR暴露SRM 2975後RMSSD變化 70
圖 4-1-13 十三至十五週齡之SHR暴露A-DEP後心跳速率變化 71
圖 4-1-14 十三至十五週齡之SHR暴露A-DEP後adjusted SDNN變化 72
圖 4-1-15 十三至十五週齡之SHR暴露A-DEP後RMSSD變化 73
圖 4-1-16 SRM 2975及A-DEP對十三至十五週齡SHR 心跳速率之影響 74
圖 4-1-17 SRM 2975及A-DEP對十三至十五週齡SHR adjusted SDNN之影響 74
圖 4-1-18 SRM 2975及A-DEP對十三至十五週齡SHR RMSSD之影響 75
圖 4-2-1 實驗動物暴露14nm ultrafine carbon black後心跳速率變化…………………...76
圖 4-2-2 實驗動物暴露14nm ultrafine carbon black後adjusted SDNN變化 77
圖 4-2-3 實驗動物暴露14nm ultrafine carbon black後RMSSD變化 78
圖 4-2-4 14 nm ultrafine carbon black對實驗動物心跳速率之影響 79
圖 4-2-5 14 nm ultrafine carbon black對實驗動物adjusted SDNN之影響 79
圖 4-2-6 14 nm ultrafine carbon black對實驗動物RMSSD之影響 80
圖 4-2-7 實驗動物暴露14nm及95nm carbon black後心跳速率變化 81
圖 4-2-8 實驗動物暴露14nm及95nm carbon black後adjusted SDNN變化 82
圖 4-2-9 實驗動物暴露14nm及95nm carbon black後RMSSD變化 83
圖 4-2-10 14 nm及95nm碳黑對實驗動物心跳速率之影響 84
圖 4-2-11 14 nm及95nm碳黑對實驗動物adjusted SDNN之影響 84
圖 4-2-12 14 nm及95nm碳黑對實驗動物RMSSD之影響 85
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詹長權等,微粒空氣污染健康風險評估計畫期末報告。EPA-90-FA11-03-91DF02,2002。
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