研究微粒帶電性質與呼吸毒性之關聯: 以小鼠暴露奈米黑碳微粒實驗為例

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研究生：	沈妤芳 Yu-Fang Shen
論文名稱：	研究微粒帶電性質與呼吸毒性之關聯: 以小鼠暴露奈米黑碳微粒實驗為例 Inhalation Exposure Study of Soot Nanoparticles with Positive, Neutral and Negative Charges in Mice
指導教授：	蕭大智 Ta-Chih Hsiao
口試委員:
學位類別：	碩士 Master
系所名稱：	工學院 - 環境工程研究所 Graduate Institute of Environmental Engineering
論文出版年：	2015
畢業學年度：	104
語文別：	中文
論文頁數：	115
中文關鍵詞：	帶電微粒、呼吸暴露、奈米黑碳微粒
外文關鍵詞：	Charged particles, Inhalation exposure, Soot Nanoparticles
相關次數：	點閱：13 下載：0
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黑碳是交通汙染源的指標之一，由於其不規則的構形易夾帶有機物、無機物甚至是有毒物質，若人體長期吸入會增加致癌率。近年來，許多研究探討暴露在奈米黑碳微粒環境下對於健康的影響，但針對帶電微粒所導致的健康傷害目前尚未有清楚的了解，因此本研究針對帶電奈米黑碳微粒對於呼吸道健康進行研究，並建立一套穩定的奈米黑碳微粒暴露系統。實驗將BALB/c雌性小鼠暴露於奈米黑碳微粒且分為帶正電與帶負電兩組，每組各有四種條件，分別為高濃度、低濃度、電性中和及HEPA控制組，每日暴露八小時且持續一周。利用電移動度分析儀 (DMA) 篩選微粒粒徑為70 nm，後端以電移動度掃描分徑器 (SMPS) 確認篩選粒徑、奈米微粒表面積偵測器 (NSAM) 量測微粒沉積在肺部的表面積、氣膠電流計 (AE) 確認微粒的電性、黑碳監測儀 (AE31)量測黑碳濃度與同時收集濾紙進行成份與構形分析。綜合以上儀器可隨時監測系統的穩定性，並且相互比較量測值的準確性。暴露後一週犧牲並收集小鼠的肺部灌洗液、血液與肺部組織，評估發炎反應與肺部組織的破壞程度 (BALF Total Protein、BALF LDH、Serum IL-6、Lung 8-Isoprostane、Lung Caspase-3、Lung BPDE)。BALF-LDH、Lung 8-Isoprostane、 Serum IL-6皆與黑碳的質量濃度、肺部沉積表面積濃度與電流量有良好的線性關係。尤其BALF-LDH的分析具有最佳的相關性，並可觀察出在低暴露劑量的範圍下，比起正電與電性中和黑碳奈米微粒，負電黑碳奈米微粒所造成的生物毒性較低。

Soot particle is one of the indicators of traffic pollution. It can contain organic, inorganic or even toxic substances easier due to its irregular structure. Exposure to soot particle significantly increased the risk of lung cancer. In recent years, many studies investigate the health effects after exposure to soot particles, but for the charged particles is not clear understanding yet. Therefore, this study establish a stable soot particle exposure system and study the biological responses of mouse after exposing to the charged soot particles. BALB/c female mice were exposed to soot particles into positively and negatively charged groups, each have four conditions (high concentration, low concentration, electrical and control group), and exposed for eight hours a day and last for a week. Soot particle size were select 70 nm by Differential Mobility Analyze (DMA) and confirm particle size by Scanning Mobility Particle Sizer (SMPS), Nanoparticle Surface Area Monitor (NSAM) measure the surface area of the particles deposited in the lungs, Aerosol Electrometer (AE) confirm the electric charge of particles, Aethalometer (AE31) and Optical Transmissometer (OT21) measure the concentration of soot particle. At the same time, filter were collect soot particle for composition and structure analysis. Based on the above instruments, they can monitor the stability of the system and the compare the accuracy of the measurement data. After exposure, we collected lung tissue, serum and bronchoalveolar lavage fluid of mouse to study the biological responses (BALF-Total Protein、BALF-LDH、Serum-IL-6、Lung-8-Isoprostane、Lung-Caspase-3、Lung-BPDE). The levels of BALF-LDH, Lung 8-Isoprostane and Serum IL-6 are well linearly correlated to BC mass concentration, lung deposition surface area concentration and charge current. Especially for BALF-LDH, the correlations are almost perfect linear. Furthermore, the responses for negative charged soot particles are significantly lower than both neutral and positive charge particles (especially in low exposure dosage range).

摘要    I
Abstract    II
目錄    IV
圖目錄    VII
表目錄    IX
第一章 前言    1
1-1研究動機    1
1-2研究目的    2
第二章 文獻回顧    3
2-1奈米微粒的生物毒性    3
2-1-1 微粒粒徑    3
2-1-2 微粒構形    5
2-1-3 微粒電性    6
2-2奈米微粒的健康效應    8
2-3黑碳的特性    10
2-3-1 黑碳的來源    10
2-3-2 黑碳的形成    13
2-3-3 黑碳的毒性    17
2-4黑碳的健康效應    21
2-4-1 交通汙染源    21
2-4-2 職業傷害    22
2-4-3 實驗室暴露    23
第三章 研究方法    24
3-1研究架構    24
3-2實驗流程    24
3-3研究設計    25
3-4暴露實驗    26
3-3-1 產生源系統    27
3-3-2 篩分系統    34
3-3-3 暴露系統    34
3-3-4 量測系統    37
3-4毒理分析    39
3-4-1以Bradford 法進行肺部灌洗液蛋白質定量    40
3-4-2肺部灌洗液與乳酸脫氫酶LDH評估    41
3-4-3血液與細胞激素IL-6    41
3-4-4以Bradford 法進行肺部組織蛋白質定量    43
3-4-5肺部組織與氧化壓力    44
3-4-6肺部組織與Caspase-3    45
3-4-7肺部組織與BPDE    46
3-4統計分析    47
3-5濾紙分析    48
第四章 結果與討論    51
4-1量測結果    51
4-1-1 系統的穩定性與燃燒狀態    51
4-1-2 微粒沉積在肺部的表面積濃度    57
4-1-3 微粒構形與電性    59
4-1-4 微粒成分與毒性分析    63
4-2毒理分析    70
4-2-1 肺部灌洗液毒理分析 (Total protein、LDH)    70
4-2-2 血液毒理分析 (IL-6)    72
4-2-3 肺部組織毒理分析(8-Isoprostane、Caspase-3、BPDE)    72
4-2-4 小鼠體重分析    75
4-2-5 小鼠病理切片分析    76
4-3結果討論    78
4-3-1 微粒沉積於肺部的表面積對於呼吸毒理的關聯性    78
4-3-2 微粒電性對於呼吸毒理的關聯性    80
4-3-3 微粒成分對於呼吸毒理的關聯性    83
4-3-4 多元迴歸    87
第五章 結論    90
5-1 系統狀態    90
5-2微粒構形及成分    90
5-3毒理分析    91
5-4量測結果與毒理分析之關聯性    91
參考文獻    92
附錄    97
口試委員意見回覆    100

                                

1. Schwartz, J., D.W. Dockery, and L.M. Neas, Is daily mortality associated specifically with fine particles? Journal of the Air & Waste Management Association, 1996. 46(10): p. 927-939.
2. Dockery, D.W., et al., An Association between Air Pollution and Mortality in Six U.S. Cities. New England Journal of Medicine, 1993. 329(24): p. 1753-1759.
3. Berghmans, P., et al., Exposure assessment of a cyclist to PM 10 and ultrafine particles. Science of the Total Environment, 2009. 407(4): p. 1286-1298.
4. Majid, H., et al., Implementation of charged particles deposition in stochastic lung model and calculation of enhanced deposition. Aerosol Science and Technology, 2012. 46(5): p. 547-554.
5. Cohen, B.S., et al., Deposition of charged particles on lung airways. Health Physics, 1998. 74(5): p. 554-560.
6. Yu, C.P. and K. Chandra, Precipitation of submicron charged particles in human lung airways. Bulletin of mathematical biology, 1977. 39(4): p. 471-478.
7. Chan, T.L., et al., Effect of electrostatic charges on particle deposition in a hollow cast of the human larynx-tracheobronchial tree. Journal of Aerosol Science, 1978. 9(5): p. 463-468.
8. Alexandre, A., S.T. Peter, and C.W.C. Warren, The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems. Annual Review of Biomedical Engineering, 2012. 14(1): p. 1-16.
9. Lee, S.G., et al., One-pass antibacterial efficacy of bipolar air ions against aerosolized Staphylococcus epidermidis in a duct flow. Journal of Aerosol Science, 2014. 69: p. 71-81.
10. Sayes, C.M., K.L. Reed, and D.B. Warheit, Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicological Sciences, 2007. 97(1): p. 163-180.
11. ICRP, ICRP Publication 66: Human Respiratory Tract Model for Radiological Protection. 1994: Elsevier Health Sciences.
12. Oberdörster, G., E. Oberdörster, and J. Oberdörster, Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environmental health perspectives, 2005: p. 823-839.
13. Rahman, Q., et al., Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Environmental health perspectives, 2002. 110(8): p. 797.
14. Perrault, S.D., et al., Mediating tumor targeting efficiency of nanoparticles through design. Nano letters, 2009. 9(5): p. 1909-1915.
15. Gratton, S.E.A., et al., The effect of particle design on cellular internalization pathways. Proceedings of the National Academy of Sciences, 2008. 105(33): p. 11613-11618.
16. Black, K.C.L., et al., Radioactive 198Au-Doped Nanostructures with Different Shapes for In Vivo Analyses of Their Biodistribution, Tumor Uptake, and Intratumoral Distribution. ACS Nano, 2014. 8(5): p. 4385-4394.
17. George, S., et al., Surface Defects on Plate-Shaped Silver Nanoparticles Contribute to Its Hazard Potential in a Fish Gill Cell Line and Zebrafish Embryos. ACS Nano, 2012. 6(5): p. 3745-3759.
18. Cho, E.C., et al., Understanding the Role of Surface Charges in Cellular Adsorption versus Internalization by Selectively Removing Gold Nanoparticles on the Cell Surface with a I2/KI Etchant. Nano Letters, 2009. 9(3): p. 1080-1084.
19. Ehn, M., et al., Atmospheric ions and nucleation: a review of observations. Atmospheric Chemistry and Physics, 2011. 11(2): p. 767-798.
20. Maricq, M.M., Thermal equilibration of soot charge distributions by coagulation. Journal of Aerosol Science, 2008. 39(2): p. 141-149.
21. Maricq, M.M., On the electrical charge of motor vehicle exhaust particles. Journal of Aerosol Science, 2006. 37(7): p. 858-874.
22. Lee, E.S., B. Xu, and Y. Zhu, Measurements of ultrafine particles carrying different number of charges in on-and near-freeway environments. Atmospheric Environment, 2012. 60: p. 564-572.
23. Bayram, H., et al., The effect of diesel exhaust particles on cell function and release of inflammatory mediators from human bronchial epithelial cells in vitro. American Journal of Respiratory Cell and Molecular Biology, 1998. 18(3): p. 441-448.
24. Turner, J., et al., A Toxicology Suite Adapted for Comparing Parallel Toxicity Responses of Model Human Lung Cells to Diesel Exhaust Particles and Their Extracts. Aerosol Science and Technology, 2015. 49(8): p. 599-610.
25. Organization, W.H., Health Effects of Particulate Matter. World Health Organization Report, 2012.
26. Bell, M.L. and D.L. Davis, Reassessment of the lethal London fog of 1952: novel indicators of acute and chronic consequences of acute exposure to air pollution. Environmental health perspectives, 2001. 109(Suppl 3): p. 389.
27. Chen, G., et al., Traffic-related air pollution and lung cancer: A meta-analysis. Thoracic Cancer, 2015. 6(3): p. 307-318.
28. Chen, F., H. Jackson, and W.F. Bina, Lung adenocarcinoma incidence rates and their relation to motor vehicle density. Cancer Epidemiology Biomarkers & Prevention, 2009. 18(3): p. 760-764.
29. Meng, Z., G. Qin, and B. Zhang, DNA damage in mice treated with sulfur dioxide by inhalation. Environmental and molecular mutagenesis, 2005. 46(3): p. 150-155.
30. Lamarque, J.F., et al., Historical (1850–2000) gridded anthropogenic and biomass burning emissions of reactive gases and aerosols: methodology and application. Atmospheric Chemistry and Physics, 2010. 10(15): p. 7017-7039.
31. Hamins, A., Environmental implications of combustion processes. 1993.
32. Bond, T.C., et al., Historical emissions of black and organic carbon aerosol from energy‐related combustion, 1850–2000. Global Biogeochemical Cycles, 2007. 21(2).
33. Palmer, H.B. and C.F. Culis, The Formation of Carbon from Gases. Chemistry and Physics of Carbon, P. L. Walker, Ed., Vol. 1, Marcel Dekker, New York, 1965: p. 265-325
34. Flagan, R.C. and J.H. Seinfeld, Fundamentals of air pollution engineering. 2013: Courier Corporation.
35. Michael, F., Reaction mechanism of soot formation in flames. Physical Chemistry Chemical Physics, 2002. 4(11): p. 2028-2037.
36. Xi, J. and B.J. Zhong, Soot in diesel combustion systems. Chemical engineering & technology, 2006. 29(6): p. 665-673.
37. Barfknecht, T.R., Toxicology of soot. Progress in energy and combustion science, 1983. 9(3): p. 199-237.
38. Nisbet, I.C.T. and P.K. LaGoy, Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs). Regulatory Toxicology and Pharmacology, 1992. 16(3): p. 290-300.
39. Rathore, H.S., Handbook of Chromatography: Liquid Chromatography of Polycyclic Aromatic Hydrocarbons. Vol. 10. 1993: CRC Press.
40. Richter, H. and J.B. Howard, Formation of polycyclic aromatic hydrocarbons and their growth to soot—a review of chemical reaction pathways. Progress in Energy and Combustion science, 2000. 26(4): p. 565-608.
41. Lyon, F., IARC monographs on the evaluation of carcinogenic risks to humans. 2014.
42. Zanobetti, A. and J. Schwartz, Air pollution and emergency admissions in Boston, MA. Journal of epidemiology and community health, 2006. 60(10): p. 890-895.
43. Peters, A., et al., Exposure to traffic and the onset of myocardial infarction. New England Journal of Medicine, 2004. 351(17): p. 1721-1730.
44. Delfino, R.J., et al., Traffic-related air pollution and blood pressure in elderly subjects with coronary artery disease. Epidemiology (Cambridge, Mass.), 2010. 21(3).
45. Klot, S.v., et al., Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Circulation, 2005. 112(20): p. 3073-3079.
46. Peters, A., et al., Increased particulate air pollution and the triggering of myocardial infarction. Circulation, 2001. 103(23): p. 2810-2815.
47. Klot, S.V., et al., Estimated personal soot exposure is associated with acute myocardial infarction onset in a case-crossover study. Progress in cardiovascular diseases, 2011. 53(5): p. 361-368.
48. Collins, J.F., et al., Risk assessment for benzo [a] pyrene. Regulatory toxicology and pharmacology, 1991. 13(2): p. 170-184.
49. Rouse, R.L., et al., Soot nanoparticles promote biotransformation, oxidative stress, and inflammation in murine lungs. American journal of respiratory cell and molecular biology, 2008. 39(2): p. 198-207.
50. Gordon, T., et al., Pulmonary and cardiovascular effects of acute exposure to concentrated ambient particulate matter in rats. Toxicology Letters, 1998. 96–97: p. 285-288.
51. Chan, J.K.W., et al., Age-Specific Effects on Rat Lung Glutathione and Antioxidant Enzymes after Inhaling Ultrafine Soot. American Journal of Respiratory Cell and Molecular Biology, 2013. 48(1): p. 114-124.
52. Omari, S.B.A., K. Kawajiri, and T. Yonesawa, Soot processes in a methane-fueled furnace and their impact on radiation heat transfer to furnace walls. International journal of heat and mass transfer, 2001. 44(13): p. 2567-2581.
53. Jenny, R., et al., Effective density characterization of soot agglomerates from various sources and comparison to aggregation theory. Aerosol Science and Technology, 2013. 47(7): p. 792-805.
54. Yokelson, R.J., D.W.T. Griffith, and D.E. Ward, Open-path Fourier transform infrared studies of large-scale laboratory biomass fires. Journal of Geophysical Research: Atmospheres, 1996. 101: p. 21067.
55. Chen, W.A., et al., Particle emissions from laboratory combustion of wildland fuels: In situ optical and mass measurements. Geophysical Research Letters, 2006. 33(4).
56. Chen, W.A., et al., Emissions from laboratory combustion of wildland fuels: Emission factors and source profiles. Environmental science & technology, 2007. 41(12): p. 4317-4325.
57. Urbanski, S.P., Combustion efficiency and emission factors for wildfire-season fires in mixed conifer forests of the northern Rocky Mountains, US. Atmos. Chem. Phys., 2013. 13(14): p. 7241-7262.
58. 曾能駿, et al., 兩種不同方法產生的奈米銀微粒之形態特性分析. 勞工安全衛生研究季刊, 2014.
59. Adachi, K., S.H. Chung, and P.R. Buseck, Shapes of soot aerosol particles and implications for their effects on climate. Journal of Geophysical Research: Atmospheres (1984–2012), 2010. 115(D15).
60. Maricq, M.M. and N. Xu, The effective density and fractal dimension of soot particles from premixed flames and motor vehicle exhaust. Journal of Aerosol Science, 2004. 35(10): p. 1251-1274.
61. Köylü, Ü.Ö., et al., Fractal and projected structure properties of soot aggregates. Combustion and Flame, 1995. 100(4): p. 621-633.
62. Kim, D., et al., Environmental aging of polycyclic aromatic hydrocarbons on soot and its effect on source identification. Chemosphere, 2009. 76(8): p. 1075-1081.
63. Li, X.Y., et al., Short-term inflammatory responses following intratracheal instillation of fine and ultrafine carbon black in rats. Inhalation toxicology, 1999. 11(8): p. 709-731.
64. Stoeger, T., et al., Instillation of six different ultrafine carbon particles indicates a surface area threshold dose for acute lung inflammation in mice. Environmental health perspectives, 2006: p. 328-333.

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