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研究生:林映君
研究生(外文):Yin-Jyun Lin
論文名稱:臭氧對健康大鼠心血管生理指標之影響
論文名稱(外文):Alterations of physiological cardiovascular markers in rats exposed to ozone
指導教授:鄭尊仁 教授
指導教授(外文):Tsun-Jen Cheng
口試委員:陳保中 教授蘇大成 教授陳主智 教授
口試日期:2012-07-09
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:2012
畢業學年度:100
語文別:中文
論文頁數:82
中文關鍵詞:臭氧血壓心率變異性
外文關鍵詞:Ozoneblood pressureheart rate variability
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流行病學研究發現空氣污染會增加肺部及心血管疾病的死亡率及住院率。空氣汙染可能透過影響自主神經系統的平衡或氧化壓力和發炎反應,引起心血管的健康效應,血壓、心跳和心律變異性是心血管的重要指標,但空氣汙染對其影響機制仍有待探討。目前很多空氣汙染研究探討微粒的健康效應,發現微粒會使心跳、血壓上升,及降低心律變異性,但在其他空氣汙染物如臭氧的研究並不多,少數流行病學研究發現臭氧對血壓、心跳及心律變異性有延遲及累積效應,但主要是觀察到天的影響,而未有更短時間如一天以內的研究,因此本研究想探討臭氧對大鼠心血管生理指標是否有急性的累積及延遲的效應。
我們用WKY健康大鼠,利用改裝的空氣汙染物暴露系統導入外界大氣,以交叉方式進行暴露,每次暴露為期一週,使動物暴露於經過HEPA過濾不含微粒之外界大氣,實驗動物分別經過兩次的空氣汙染物暴露。我們利用生理遙測系統連續收集實驗動物的收縮壓、舒張壓、心跳及心電圖資料,並同時監測臭氧、和溫度,計算每小時心血管生理指標和暴露資料的平均值,利用1至7天的移動平均值 (Moving average)、0至6天的單日延遲 (Single lag)、1至48小時的移動平均值和0至48小時的單小時延遲臭氧濃度做為不同的暴露情形。統計分析先經過生理週期的處理後,以混和效應模式 (Mixed effects model)來評估臭氧的心血管效應。
本研究發現接近大氣濃度的臭氧暴露會對心血管生理指標有天或小時的延遲和累積效應。在天的效應中,當天的臭氧暴露會使收縮壓、脈壓顯著增加,且具延遲及累積效應,但會使心律變異性時域指標 (SDNN和RMSSD)上升。在小時的效應中,臭氧暴露會顯著增加大鼠收縮壓、舒張壓和脈壓,並降低心律變異性,此效應最快在5至8小時內可看到,且具累積或延遲的效應,但本研究無法排除其他氣狀汙染物暴露對心血管效應可能的貢獻,未來需要更進一步研究探討臭氧對心血管的影響。
過去流行病學研究觀察到臭氧有天的心血管效應,而本研究除了發現臭氧短期 (1-7天)的效應外,也發現臭氧更快的心血管效應 (24小時),顯示空氣汙染對心血管生理指標會有更急性的影響。

Epidemiology studies have shown that exposure to ambient air pollutants increase cardiovascular morbidity and mortality. Air pollution may alter ANS balance or promote systemic inflammation and oxidative stress and subsequently cause cardiovascular effects. Both blood pressure (BP), heart rate (HR) and heart rate variability (HRV) are important physiological markers for cardiovascular diseases. However, the precise mechanisms of air pollution mediated cardiac effects are still unclear. Most air pollution studies demonstrate the effects of particulate matter. Many results support that PM2.5 exposure can elevate BP, HR, and decrease HRV, but data of ozone effect are limited. Recently, more and more epidemiology studies found the association between BP and ozone. Increase ozone level will increase blood pressure both in lag and moving average model in epidemiological studies. These studies examine the effects base on the exposure greater than one day. It is not clear whether brief exposure to ozone at ambient level affects BP, HR and HRV.
Therefore, this study is designed to determine ozone effects on physiological cardiovascular markers. WKY rats were exposed to ambient air through a modified exposure system in Taipei from December, 2011 to February, 2012. Each rat was exposed to HEPA filtered air for two weeks. We measured SBP, DBP, HR, SDNN and RMSSD using radiotelemetry system. Association between hourly ozone level and physiological markers were examined using mixed effect model. We further used both single-lag model (0 day to 6 day or 0 hour to 48 hour) and moving-average model (1 day to 7 days or 1 hour to 48 hours mean) to estimate ozone daily and hourly lag or cumulative effects on physiological cardiovascular markers.
Our results found that environmentally relevant ambient level of ozone were associated with small increase both in day and hourly lag or moving average models. In day lag and moving average models, ozone significantly increased SBP and pulse pressure (PP) in current day and in cumulative models, but there was an increase in SDNN and RMSSD. In hourly lag models, ozone exposure significantly increased SBP, DBP, PP and decreased SDNN and RMSSD. The responses of SBP were observed within 5 to 8 hour in lag model, and also increased in hourly moving average models. Because rat was exposed to HEPA filtered air, we can not exclude effects of other gas pollutants such as nitrogen dioxide and carbon monoxide. Further studies of ozone cardiovascular effects on these cardiovascular markers are necessary.
Previous studies have shown the effects of air pollution greater than one day. Our findings suggest that in addition to day effects, air pollution could rapidly affect cardiovascular within hours.

中文摘要.................................................1
Abstract...............................................3
第一章 前言與研究目的......................................5
第二章 文獻回顧...........................................6
2.1 空氣汙染的心血管效應...................................6
2.2 臭氧的健康效應........................................7
2.2.1 臭氧與心血管生理指標的流行病學研究......................9
2.2.2 臭氧與心血管生理指標的人體實驗.........................10
2.2.3 臭氧與心血管生理指標的動物實驗.........................11
2.2.4 臭氧影響心血管生理指標的可能機制.......................18
第三章 材料與方法.........................................20
3.1 實驗流程............................................20
3.2 實驗動物............................................20
3.3 空氣汙染物暴露系統....................................21
3.4 暴露資料監測.........................................21
3.5 心血管生理指標量測....................................21
3.6 統計分析............................................22
3.6.1 資料處理...........................................22
3.6.2 控制生理週期之混和效應模式.............................23
3.6.3 臭氧延遲及累積效應...................................24
第四章 結果..............................................26
4.1 心血管生理指標原始資料................................26
4.2 暴露資料............................................26
4.3 溫度對血壓之影響.....................................26
4.4 臭氧對各心血管生理指標之天的延遲及累積效應................27
4.5 臭氧對各心血管生理指標之小時的延遲及累積效應...............28
第五章 討論...............................................30
5.1 控制生理週期之統計模式.................................30
5.2 臭氧對血壓的影響......................................31
5.3 臭氧對心律變異性的影響.................................34
5.4 臭氧對白天和夜晚心血管生理指標之效應......................34
5.5 空氣汙染物暴露系統....................................35
5.5.1 暴露系統臭氧濃度.....................................35
5.5.2 其他氣態汙染物的影響..................................36
5.6 研究優點與限制........................................37
5.7 結論與建議...........................................38
第六章 參考文獻............................................39
附錄.....................................................47

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