(18.207.240.230) 您好!臺灣時間:2020/07/09 10:58
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
本論文永久網址: 
line
研究生:李偉量
研究生(外文):Wei-Liang Li
論文名稱:大氣微粒對心肌受損大鼠之心血管毒性研究
論文名稱(外文):Cardiovascular Toxicity of Ambient Particles in Rats with Myocardial Injury
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:2008
畢業學年度:96
語文別:中文
論文頁數:63
中文關鍵詞:心臟衰竭心肌損傷超音波BNPTroponin I大氣濃縮微粒細粒徑微粒濃縮器
外文關鍵詞:Heart failureMyocardial injuryEchocardiographyBNPTroponin ICAPsUFPC
相關次數:
  • 被引用被引用:1
  • 點閱點閱:203
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
流行病學研究指出,大氣微粒會造成心臟衰竭住院率及死亡率的上升。但探討微粒與心臟衰竭相關相關性之毒理研究仍相當有限。因此本研究欲針對心室受損之大鼠暴露在大氣微粒的心臟毒性進行探討。
本研究可概分為兩大部分
第一部分:利用氣管灌注的方式,將注射isoproterenol後產生心肌損傷大鼠,分別在一周及八周後暴露大氣PM2.5微粒、PM10微粒及生理食鹽水之控制組,以心臟超音波觀察其心臟的急性及慢性效應。研究結果未呈現一致性的微粒急性效應;此外,微粒的慢性效應在本研究中也未發現。但由於測量工具及研究設計部分之限制,暴露大氣微粒是否造成心肌受損大鼠心室功能下降之效應及其詳細機轉,仍待未來研究深入探討之。
第二部分:以細粒徑微粒濃縮器進行微粒的長期暴露,利用心肌損傷後大鼠亞慢性暴露大氣濃縮微粒的心臟毒性,並檢視該濃縮微粒系統長期使用之效能及穩定性。將注射isoproterenol後產生心肌損傷大鼠三天後進行全身性呼吸暴露,以吸入大氣濃縮微粒為暴露組,呼吸過濾空氣之實驗動物為對照組,進行為期一個月、每周四天,每天五小時的連續暴露,並分別在暴露前、暴露後兩周及四周後進行尾部靜脈採血測定心肌損傷及心臟衰竭程度。研究結果發現,大氣濃縮微粒暴露會使心臟衰竭功能指標BNP較慢恢復到穩定值,但心肌損傷指標cTnI卻無發現這樣的結論,顯示大氣微粒可能在急性暴露下會有毒性效應,但其詳細作用時間及機轉仍待未來研究進一步探討。
Numerous epidemiologic studies have shown that the mortality and hospital admissions of heart failure are associated with ambient particle. However, the toxicological researches on the relationship between ambient particle and heart failure are limited. Thus, we used an animal model of myocardial injury to investigate the cardiovascular toxicity of ambient particle.
Our study are composed of two major parts:
Part Ⅰ:Rats were received 150 mg/kg isoproterenol by subcutaneous injection to induce myocardial injury. Then, rats were exposed to PM2.5、PM10 and saline by intratracheal instillation one and eight weeks after the injection of ISO. The acute and chronic cardiovascular effects were observed using echocardiography. The results showed that acute PM2.5 exposure would lead to decreased LV function, but the similar effects were not observed in PM10. Further, we didn’t observe chronic effect of particles. Because of limitations of echocardiography and study design, the exact relationship between ambient particle and heart failure need further study.
Part Ⅱ:Ultrafine particle concentrator (UFPC) was used to conduct a subchronic exposure in rats administered with 150 mg/kg of isoproterenol by subcutaneous injection. Animals were exposed to concentrated ambient particles (CAPs) for 5-hr/day, 4-day/week for 4-weeks, and controls were exposed to filtered air (FA). BNP for left ventricular function status and cTnI for myocardial injury were measured before exposure, 2 and 4 weeks after exposure. Results of BNP concentration suggest that animals exposed to CAPs may return to normal level later than FA group. As to cTnI, PM didn’t induce further myocardial injury at both CAPs and FA group. Our results suggest that CAPs may cause LV dysfunction shortly after myocardial injury.
致謝 I
目錄 II
表目錄 IV
圖目錄 V
摘要 1
Abstract 2
一、研究目的 4
二、文獻探討 5
2-1 微粒流行病學研究 5
2-2 粒狀空氣污染物的心血管健康效應 6
2-3 微粒易感受性族群 6
2-4 心臟衰竭 6
2-5 心臟衰竭之病生理 7
2-6 微粒導致心衰竭之流行病學與毒理學研究 7
2-7急性心肌梗塞與微粒空氣汙染 8
2-8 濃縮大氣微粒的健康相關研究 9
2-9 氣管灌注與呼吸暴露方式比較 10
2-10 細粒徑微粒濃縮器 10
2-11 心臟衰竭疾病動物模式 11
2-12 心臟衰竭及心肌損傷評估指標 12
2-12-1 心臟超音波 12
2-12-2 Brain Natriuretic Peptide, BNP 12
2-12-3 Troponin 13
三、氣管灌注大氣微粒對心肌受損大鼠之左心室功能研究 14
3-1 摘要 15
3-2 背景 16
3-3 材料與方法 17
3-3-1 實驗動物 17
3-3-2 微粒蒐集與製備 17
3-3-3 實驗流程 18
3-3-4 氣管內灌注(Intratracheal Installation, IT)暴露模式 18
3-3-5 心臟超音波 18
3-3-6 統計分析 19
3-4 結果 20
3-4-1 實驗動物基本特性及心臟肥大程度 20
3-4-2 微粒急性效應 20
3-4-3 微粒慢性效應 20
3-5 討論 22
3-6 結論與建議 25
3-7 表格與圖片 26
四、亞慢性呼吸暴露大氣微粒對心肌受損大鼠之心血管效應 34
4-1 摘要 35
4-2 背景 36
4-3 材料與方法 37
4-3-1 UFPC細粒徑微粒濃縮器 37
4-3-2 全身暴露系統 (Whole-Body Exposure System) 37
4-3-3 實驗流程 38
4-3-4 BNP與Troponin之測定 38
3-4-5 統計分析方法 38
4-4 結果 39
4-4-1 UFPC系統 39
4-4-2 全身暴露系統 39
4-4-3 實驗動物基本特性 39
4-4-4 BNP 40
4-4-5 Troponin I 40
4-5 討論 41
4-6 結論與建議 45
4-7 表格與圖片 46
五、參考文獻 56
Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, et al. 1996. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 335:1342-1350.
Babuin L, Jaffe AS. 2005. Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ. 173:1191-1202
Birmili W, Allen AG, Bary F, Harrison RM. 2006. Trace metal concentrations and water solubility in size-fractionated atmospheric particles and influence of road traffic. Environ Sci Technol. 40:1144-1153.
Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, et al. 2004. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation. 109:2655-71.
Burnett RT, Dales R, Krewski D, Vincent R, Dann T, Brook JR. 1995. Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases. Am J Epidemiol. 142:15-22.
Cakmak S, Dales RE, Vidal CB. 2007. Air Pollution and Mortality in Chile: Susceptibility among the Elderly. Environ Health Perspect. 115:524-527.
Chang CC, Hwang JS, Chan CC, Wang PY, Cheng TJ. 2004. Effects of concentrated ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats. Inhalation Toxicology. 16:421-429.
Chang CC, Hwang JS, Chan CC, Wang PY, Hu TH, Cheng TJ. 2005. Effects of concentrated ambient particles on heart rate variability in spontaneously hypertensive heart rats. J Occup Health. 47:471-80.
Cheng TJ, Hwang JS, Wang PY, Tsai CF, Chen CY, Lin SH, et al. 2003. Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats. Environ Health Perspect. 111:147-50.
Chang CC, Tsai SS, Ho SC, Yang CY. 2005. Air pollution and hospital admissions for cardiovascular disease in Taipei, Taiwan. Environmental Research. 98:114-119.
Chen YS, Yang CY. 2005. Effects of Asian dust storm events on daily hospital admissions for cardiovascular disease in Taipei, Taiwan. Journal of Toxicology and Environmental Health. Part A 68:1457-1464.
Chen YS, Sheen PC, Chen ER, Liu YK, Wu TN, et al. 2004. Effects of Asian dust storm events on daily mortality in Taipei, Taiwan. Environmental Research. 95:151-155.
Choi JH, Xu QS, Park SY, Kim JH, Hwang SS, Lee KH, et al. 2007. Seasonal variation of effect of air pollution on blood pressure. Epidemiol Community Health. 61:314-318.
Chuang KJ, Chan CC, Su TC, Lee CT, Tang CS. 2007. Urban air pollution on inflammation, oxidative stress, coagulation and autonomic dysfunction in young adults. AJRCCM. 15;176:370-6.
Dales R, Liu L, Szyszkowicz M, Dalipaj M, Willey J, Kulka R, et al. 2007. Particulate air pollution and vascular reactivity: the bus stop study. Int Arch Occup Environ Health. 81:159-64.
De Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, et al. 2001. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Eng J Med. 345:1014-1021.
Devlin RB, Chio AJ, Kehrl H, Sanders G,Cascio W. 2003. Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability. Eur Respir J. 21: Suppl. 40, 76s-80s.
Dockery DW, Pope CA, Xu X, Spengler JD, Ware JH, Fay ME, et al. 1993. An Association between Air Pollution and Mortality in Six U.S. Cities. N Engl J Med. 329:1753-1761.
Dockery DW. 2001. Epidemiologic evidence of cardiovascular effects of particulate air pollution. Environ Health Perspect. 109:483-486.
Ghio AJ, kim C, Delvin RB. 2000. Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. Am J Respir Crit Care Med. 162:981-988
Gibson HL, Suh HH, Coull BA, Dockery DW, Sarnat SE, Schwartz , et al. 2006. Effects of Air Pollution on Heart Rate Variability in Senior Adults in Steubenville, Ohio. JOEM. 48:780-788.
Goldberg MS, Burnett RT, Bailar JC III, et al. 2001. The association between daily mortality and ambient air particle pollution in Montreal, Quebec. 2. Cause-specific mortality. Environ Res. 86:26-36.
Gong Jr H, Linn WS, Sioutas C, Terrell SL, Clark KW, Anderson KR. 2003. Controlled exposures of healthy and asthmatic volunteers to concentrated ambient fine particles in los angeles. Inhalation Toxicology. 15:305-325.
Gryparis A, Forsberg B, Katsouyanni K, Analitis A, Touloumi G, Schwartz J, et al.2004. Acute Effects of Ozone on Mortality from the “Air Pollution and Health: A European Approach” Project. Am J Respir Crit Care Med. 170:1080-1087.
Gurgueira SA, Lawrence J, Coull B, Murthy GGK, González-Flecha B. 2002. Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ Health Perspect. 110:749-755.
Hama N, Itoh H, Shirakami G, Nakagawa O, Suga S, Ogawa Y, et al. 1995. Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation. 92:1558-1564.
Hoek G, Brunekreef B, Fischer P, van Wijnen J. 2001. sociation between air pollution and heart failure, arrhythmia, embolism, thrombosis, and other cardiovascular causes of death in a time series study. Epidemiology. 12:355-361.
Janssen NAH, Schwartz J, Zanobetti A, Suh HH. 2002. Air Conditioning and Source-Specific Particles as Modifiers of the Effect of PM10 on Hospital Admissions for Heart and Lung Disease. Environ Health Perspect. 110:43-49.
Kwon HJ, Cho SH, Nyberg F, Pershagen G. 2000. Effects of ambient air pollution on daily mortality in a cohort of patients with congestive heart failure. Epidemiology. 12:413-419.
Lanki T, Pekkanen J, Aalto P, Elosua R, Berglind N, D’Ippoliti D, et al. 2006. Associations of traffic related air pollutants with hospitalisation for first acute myocardial infarction: the HEAPSS study. Occup Environ Med. 63:844-851.
Lei YC, Chan CC, Wang PY, Lee CT, Cheng TJ. 2004. Effects of Asian dust event particles on inflammation markers in peripheral blood and bronchoalveolar lavage in pulmonary hypertensive rats. Environmental Research. 95:71-76.
Lippmann M. 2005. Special Issue: Effects of subchronic exposure to concentrated ambient particles. Inhalation Toxicology. 17:177-261.
Maisel A, Krishnaswamy P, Novak RM, Mccord J, Hollander JE, Duc P, et al. Rapid measurement of b-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 347:161-167.
McClellan RO, Henderson RF. Concepts in Inhalation Toxicology. 2nd ed., Washington, DC: Taylor & Francis, 1995; 1-638.
Muders F, Elsnere D. 2000. Animal Models of Chronic Heart Failure. Pharmacol Res. 43:605-612.
Nadziejko C, Fang K, Narciso S, Zhong M, Su WC, Gordon T. 2004. Effect of Particulate and Gaseous Pollutants on Spontaneous Arrhythmias in Aged Rats. Inhalation Toxicology. 16:373-380.
Okuda N, Hayashi T, Mori T, Inamoto S, Okabe Ostro B, Broadwin R, Green S, Feng WY, Lipsett M. 2006. Fine Particulate Air Pollution and Mortality in Nine California Counties: Results from CALFINE. Environ Health Perspect. 114:29-33.
Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Klonere RA, et al. 1979. Myocardial infarct size and ventricular function in rats. Circ Res. 44:503-512.
Richards AM, Nicholls MG, Espiner EA, Lainchbury EG, Troughton RW, Elliott J, et al. 2003. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation. 107:2786-2792.
Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. 2007. Heart Disease and Stroke Statistics—2007 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 115:e69-e171.
Salma I, Maenhaut W. 2006. Changes in elemental composition and mass of atmospheric aerosol pollution between 1996 and 2002 in a Central European city. Environ. Pollut. 143:479-88.
Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. 2000. Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994. N Engl J Med. 343:1742-1749.
Schwartz J, Litonjua A, Suh H, Verrier M, Zanobetti A, Syring M, et al. 2005. Traffic related pollution and heart rate variability in a panel of elderly subjects. Thorax. 60:455-461.
Sirivelu MP., MohanKumar SMJ, Wagner JG, Harkema JR, MohanKumar PS. 2006. Activation of the Stress Axis and Neurochemical Alterations in Specific Brain Areas by Concentrated Ambient Particle Exposure with Concomitant Allergic Airway Disease. Environ Health Perspect. 114:870-874.
Sjaastad I, Sejersted OM, Ilebekk A, Bjornerheim R. 2000. Echocardiographic criteria for detection of postinfarction congestive heart failure in rats. J Appl Physiol. 89:1445-1454.
Symons J M, Wang L, Guallar E, Howell E, Dominici F, Schwab M, et al. 2006. A Case-Crossover Study of Fine Particulate Matter Air Pollution and Onset of Congestive Heart Failure Symptom Exacerbation Leading to Hospitalization. Am J Epidemiol. 164:421-33.
Teerlink JR, Pfeffer JM, Pfeffer MA. 1994. Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats. Circ Res. 75:105-113.
Tertre AL, Medina S, Samoli E, Forsberg B, Michelozzi P, Boumghar A, et al. 2002. Short-term effects of particulate air pollution on cardiovascular diseases in eight European cities. J Epidemiol Community Health. 56:773-779.
The Joint European Society of Cardiology/American College of Cardiology Committee. 2000. Myocardial infarction redefined — A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. European Heart Journal. 21:1502-1513
Von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D’Ippoliti D, et al. 2005. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five european cities. Circulation. 112;3073-3079.
Wellenius GA, Bateson TF, Mittleman MA, Schwartz J. 2005. Particulate air pollution and the rate of hospitalization for congestive heart failure among Medicare beneficiaries in Pittsburgh, Pennsylvania. Am J Epidemiol. 161:130-136.
Wellenius GA, Coull BA, Godleski JJ, Koutrakis P, Okabe K, Savage, ST. 2003. Inhalation of Concentrated Ambient Air Particles Exacerbates Myocardial Ischemia in Conscious Dogs. Environ Health Perspect. 111:402-408.
Wellenius GA, Schwartz J, Mittleman MA. 2006. Particulate air pollution and hospital admissions for congestive heart failure in seven United States Cities. Am J Cardiol. 97:404-408.
Wong TW, Lau TS, Yu TS, Neller A, Wong SL, Tam W, et al. 1999. Air pollution and hospital admissions for respiratory and cardiovascular diseases in Hong Kong. Occup Environ Med. 56:679-683.
Yan YH, Huang CH, Chen WJ, Wu MF, Cheng TJ. 2008. Effects of diesel exhaust particles on left ventricular function in isoproterenol-induced myocardial injury and healthy rats. Inhalation Toxicology. 20:199-203.
Yang CY, Tsai SS, Chang CC, HoSC. 2005. Effects of Asian Dust Storm Events on Daily Admissions for Asthma in Taipei, Taiwan. Inhalation Toxicology. 17:817- 821.
Yang CY, Chen YS, Chiu HF, Goggins WB. 2005. Effects of Asian dust storm events on daily stroke admissions in Taipei, Taiwan. Environmental Research. 99:79-84.
Yue W, Schneider A, St¨olzel M, R¨uckerl R, Cyrys J, Pan X. 2007. Ambient source-specific particles are associated with prolonged repolarization and increased levels of inflammation in male coronary artery disease patients. Mutat Res: Fundam Mol Mech Mutagen. 621:50-60.
Zanobetti A, Schwartz J. 2006. Air pollution and emergency admissions in Boston, MA. J. Epidemiol. Community Health. 60:890-895.
Zanobetti A, Schwartz J. 2007. Particulate Air Pollution, Progression, and Survival after Myocardial Infarction. Environ Health Perspect. 115:769-775.
Zeka A, Sullivan JR, Vokonas PS, Sparrow D, Schwartz J. 2006. Inflammatory markers and particulate air pollution: characterizing the pathway to disease. International Journal of Epidemiology. 35:1347-1354.
石宜鑫、王鵬堯:超細粒徑微粒濃縮器操作介面之改善與自動化之研究。國立中央大學 2001.
黃于芳、鄭尊仁:微粒空氣污染物對心臟功能不全大鼠之心血管研究。國立台灣大學 2007.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔