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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82172完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉興華(Shing-Hwa Liu) | |
| dc.contributor.author | Pei-Chen Chen | en |
| dc.contributor.author | 陳珮甄 | zh_TW |
| dc.date.accessioned | 2022-11-25T06:33:10Z | - |
| dc.date.copyright | 2021-08-31 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-09 | |
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Mishra, 'Oxidative stress, mitochondrial damage and diabetic retinopathy,' Biochim Biophys Acta, vol. 1852, no. 11, pp. 2474-83, 2015. 23. Y. T. Wang, H. C. Lin, W. Z. Zhao, H. J. Huang, Y. L. Lo, H. T. Wang, and A. M. Lin, 'Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death,' Sci Rep, vol. 7, pp. 45741, 2017. 24. Dmitriy Matveychuk, Serdar M. Dursun, Paul L. Wood, and Glen B. Baker, 'Reactive Aldehydes and Neurodegenerative Disorders ' Bulletin of Clinical Psychopharmacology, 2011. 25. R. J. Henning, G. T. Johnson, J. P. Coyle, and R. D. Harbison, 'Acrolein Can Cause Cardiovascular Disease: A Review,' Cardiovasc Toxicol, vol. 17, no. 3, pp. 227-236, 2017. 26. A. G. Feroe, R. Attanasio, and F. Scinicariello, 'Acrolein metabolites, diabetes and insulin resistance,' Environ Res, vol. 148, pp. 1-6, 2016. 27. S. M. Cohen, E. M. Garland, M. St John, T. Okamura, and R. A. Smith, 'Acrolein initiates rat urinary bladder carcinogenesis,' Cancer Res, vol. 52, no. 13, pp. 3577-81, 1992. 28. P. A. Monach, L. M. Arnold, and P. A. Merkel, 'Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review,' Arthritis Rheum, vol. 62, no. 1, pp. 9-21, 2010. 29. A. Moghe, S. Ghare, B. Lamoreau, M. Mohammad, S. Barve, C. McClain, and S. Joshi-Barve, 'Molecular mechanisms of acrolein toxicity: relevance to human disease,' Toxicol Sci, vol. 143, no. 2, pp. 242-55, 2015. 30. R. Vanholder, A. Argilés, U. Baurmeister, P. Brunet, W. Clark, G. Cohen, P. P. De Deyn, R. Deppisch, B. Descamps-Latscha, T. Henle, A. Jorres, Z. A. Massy, M. Rodriguez, B. Stegmayr, P. Stenvinkel, and M. L. Wratten, 'Uremic toxicity: present state of the art,' Int J Artif Organs, vol. 24, no. 10, pp. 695-725, 2001. 31. K. Sakata, K. Kashiwagi, S. Sharmin, S. Ueda, and K. Igarashi, 'Acrolein produced from polyamines as one of the uraemic toxins,' Biochem Soc Trans, vol. 31, no. 2, pp. 371-4, 2003. 32. K. Igarashi, T. Uemura, and K. Kashiwagi, 'Acrolein: An Effective Biomarker for Tissue Damage Produced from Polyamines,' Methods Mol Biol, vol. 1694, pp. 459-468, 2018. 33. J. H. Hong, P. A. H. Lee, Y. C. Lu, C. Y. Huang, C. H. Chen, C. H. Chiang, P. M. Chow, F. S. Jaw, C. C. Wang, C. Y. Huang, T. W. Wang, J. H. Liu, and H. T. Wang, 'Acrolein contributes to urothelial carcinomas in patients with chronic kidney disease,' Urol Oncol, vol. 38, no. 5, pp. 465-475, 2020. 34. M. S. Ahmed, H. Langer, M. Abed, J. Voelkl, and F. Lang, 'The uremic toxin acrolein promotes suicidal erythrocyte death,' Kidney Blood Press Res, vol. 37, no. 2-3, pp. 158-67, 2013. 35. J. J. Creely, S. J. DiMari, A. M. Howe, and M. A. 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Donnelley, 'Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology,' Respir Res, vol. 19, no. 1, pp. 136, 2018. 44. R. C. Stone, I. Pastar, N. Ojeh, V. Chen, S. Liu, K. I. Garzon, and M. Tomic-Canic, 'Epithelial-mesenchymal transition in tissue repair and fibrosis,' Cell Tissue Res, vol. 365, no. 3, pp. 495-506, 2016. 45. R. Kalluri, and E. G. Neilson, 'Epithelial-mesenchymal transition and its implications for fibrosis,' J Clin Invest, vol. 112, no. 12, pp. 1776-84, 2003. 46. S. E. Lee, and Y. S. Park, 'Role of lipid peroxidation-derived α, β-unsaturated aldehydes in vascular dysfunction,' Oxid Med Cell Longev, vol. 2013, pp. 629028, 2013. 47. S. Pizzimenti, E. Ciamporcero, M. Daga, P. Pettazzoni, A. Arcaro, G. Cetrangolo, R. Minelli, C. Dianzani, A. Lepore, F. Gentile, and G. Barrera, 'Interaction of aldehydes derived from lipid peroxidation and membrane proteins,' Front Physiol, vol. 4, pp. 242, 2013. 48. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82172 | - |
| dc.description.abstract | "丙烯醛是個無所不在的環境汙染物，人類的暴露途徑通常是從飲食、抽菸、汽車廢氣以及體內脂質過氧化，丙烯醛也是化療藥物Cyclophosphamide 的代謝產物之一，其引發的嚴重副作用，例如：出血性膀胱炎、腎盂炎、輸尿管炎及血尿等，先前研究指出丙烯醛是個內源性的尿毒症毒素，會促使慢性腎臟病患者發生泌尿道上皮細胞癌，但目前鮮少研究針對丙烯醛造成腎臟形態與功能的影響，因此本篇研究欲探討丙烯醛是否會使腎臟產生毒性反應與潛在的作用機制為何。首先，細胞實驗中以丙烯醛10, 15, 20 μM培養大鼠腎小管上皮細胞NRK-52E細胞，經24小時後結果顯示會造成細胞凋亡以及蛋白水解酶活化，也會刺激氧化壓力產生並引起內質網壓力，其作用機制為上游的Bip蛋白表現增加，進而活化下游的IRE1α‑XBP1和eIF2α‐ATF4‐CHOP訊號途徑；另外也觀察到SMAD 2/3途徑被活化，轉錄因子Snail進入細胞核，造成細胞上皮間質轉化(epithelial-mesenchymal transition, EMT)的相關蛋白E-cadherin表現量下降、N-cadherin、Fibronectin、α-SMA、Vimentin表現量增加，加入2 mM抗氧化劑N acetyl cysteine (NAC)，預處理2.5小時後再加入acrolein，可觀察到與內質網壓力相關的訊號途徑皆被抑制。動物實驗中，給予五週齡ICR公鼠2.5, 5, 10 mg/kg/day的丙烯醛，另外三組再給予NAC，此外還有一組只給予純水當作控制組，總共七組，以管餵的方式連續給藥一個月，每週秤重兩次，四周後收集腎臟組織，以西方點墨法結果再次驗證細胞實驗，而給予丙烯醛的組別中，老鼠的血清具有較高的空腹血糖值、胰島素、三酸甘油脂以及脂質過氧化代謝物。除此之外，在組織學分析結果中，丙烯醛引起腎小球和腎小管的形態改變、腎臟纖維化，並呈現劑量依賴性，且有給予NAC的組別中皆被抑制。藉由本研究希望瞭解丙烯醛對於腎臟細胞及功能損傷之作用及可能機轉。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T06:33:10Z (GMT). No. of bitstreams: 1 U0001-0908202111110900.pdf: 6311136 bytes, checksum: cdf27482a0a5db39c164d556b22b6fa3 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員會審定書(I) 誌謝(II) 中文摘要(III) Abstract(IV) Contents(VI) List of abbreviation(VIII) Part 1: Introduction(1) 1.1 Exposure routes and metabolism of acrolein(1) 1.2 Acrolein-related toxicity and diseases(2) 1.3 Effects of acrolein on kidney(4) 1.4 Aims(5) Part 2: Materials and methods(6) 2.1 Cell culture(6) 2.2 Acrolein treatment(6) 2.3 MTT cell proliferation assay(6) 2.4 DCFDA cellular ROS detection assay(7) 2.5 Western blot analysis(7) 2.6 Animal treatment(9) 2.7 Oral glucose tolerance test (OGTT) (9) 2.8 Measurements of insulin and TBARS level in serum samples(10) 2.9 Histological staining(10) 2.10 Statistics(11) Part 3: Results(12) 3.1 Effects of cytotoxicity and apoptosis induced by acrolein in NRK-52E cells.(12) 3.2 Investigation into the mechanisms of acrolein-induced cell apoptosis.(13) 3.2.1 Acrolein causes ROS generation through the ER-mediated pathway.(13) 3.2.2 NAC inhibits acrolein-triggered ER stress.(13) 4.1 Effects of acrolein on body weight, organ weight and blood glucose in mice.(15) 4.2 Investigation into the results of ER stress in kidney after exposed to acrolein. (16) 4.3 Pathological changes caused by exposure to acrolein in mice.(16) Part 4: Discussion(18) Part 5: Conclusion(23) Part 6: Figures(24) Part 7: References(48)" | |
| dc.language.iso | en | |
| dc.subject | 氧化壓力 | zh_TW |
| dc.subject | NRK-52E | zh_TW |
| dc.subject | 丙烯醛 | zh_TW |
| dc.subject | 醛類 | zh_TW |
| dc.subject | 內質網壓力 | zh_TW |
| dc.subject | 腎上皮細胞 | zh_TW |
| dc.subject | endoplasmic reticulum stress | en |
| dc.subject | NRK-52E | en |
| dc.subject | renal epithelial cell | en |
| dc.subject | acrolein | en |
| dc.subject | aldehydes | en |
| dc.subject | oxidative stress | en |
| dc.title | 探討體內/體外丙烯醛對腎近端小管上皮細胞生長及功能的毒理作用與機制 | zh_TW |
| dc.title | Toxicological Effects and Mechanisms of Acrolein on Renal Proximal Tubular Epithelial Cell Growth and Function in vitro and in vivo | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 姜至剛(Hsin-Tsai Liu),洪冠予(Chih-Yang Tseng) | |
| dc.subject.keyword | 丙烯醛,醛類,內質網壓力,氧化壓力,腎上皮細胞,NRK-52E, | zh_TW |
| dc.subject.keyword | acrolein,aldehydes,endoplasmic reticulum stress,oxidative stress,renal epithelial cell,NRK-52E, | en |
| dc.relation.page | 57 | |
| dc.identifier.doi | 10.6342/NTU202102200 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2021-08-09 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| dc.date.embargo-lift | 2023-09-01 | - |
| 顯示於系所單位： | 毒理學研究所 | |
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