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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林?輝 | |
dc.contributor.author | Hong-Hsiang Liao | en |
dc.contributor.author | 廖泓翔 | zh_TW |
dc.date.accessioned | 2021-06-17T07:09:04Z | - |
dc.date.available | 2024-07-25 | |
dc.date.copyright | 2019-07-25 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-07-23 | |
dc.identifier.citation | 1. Graham, W. V.; Bonito-Oliva, A.; Sakmar, T. P., Update on Alzheimer's disease therapy and prevention strategies. Annual review of medicine 2017, 68, 413-430.
2. Parsons, C. G.; Danysz, W.; Dekundy, A.; Pulte, I., Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotoxicity research 2013, 24 (3), 358-369. 3. Bartus, R. T.; Dean, R. r.; Beer, B.; Lippa, A. S., The cholinergic hypothesis of geriatric memory dysfunction. Science 1982, 217 (4558), 408-414. 4. Winblad, B.; Engedal, K.; Soininen, H.; Verhey, F.; Waldemar, G.; Wimo, A.; Wetterholm, A.-L.; Zhang, R.; Haglund, A.; Subbiah, P., A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001, 57 (3), 489-495. 5. Mohs, R. C.; Doody, R.; Morris, J.; Ieni, J.; Rogers, S.; Perdomo, C.; Pratt, R., A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 2001, 57 (3), 481-488. 6. Mesulam, M., The cholinergic lesion of Alzheimer's disease: pivotal factor or side show? Learning & memory 2004, 11 (1), 43-49. 7. Parent, M. B.; Baxter, M. G., Septohippocampal acetylcholine: involved in but not necessary for learning and memory? Learning & Memory 2004, 11 (1), 9-20. 8. Craig, L. A.; Hong, N. S.; McDonald, R. J., Revisiting the cholinergic hypothesis in the development of Alzheimer's disease. Neuroscience & Biobehavioral Reviews 2011, 35 (6), 1397-1409. 9. Geula, C.; Nagykery, N.; Nicholas, A.; Wu, C.-K., Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease. Journal of Neuropathology & Experimental Neurology 2008, 67 (4), 309-318. 10. Auld, D. S.; Kornecook, T. J.; Bastianetto, S.; Quirion, R., Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies. Progress in neurobiology 2002, 68 (3), 209-245. 11. Auld, D. S.; Kar, S.; Quirion, R., β-Amyloid peptides as direct cholinergic neuromodulators: a missing link? Trends in neurosciences 1998, 21 (1), 43-49. 12. Zhang, J.; Dong, X.-P., Dysfunction of microtubule-associated proteins of MAP2/tau family in Prion disease. Prion 2012, 6 (4), 334-338. 13. Jin, M.; Shepardson, N.; Yang, T.; Chen, G.; Walsh, D.; Selkoe, D. J., Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proceedings of the National Academy of Sciences 2011, 108 (14), 5819-5824. 14. Kumar, A.; Singh, A., A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacological Reports 2015, 67 (2), 195-203. 15. Ross, C. A.; Poirier, M. A., Protein aggregation and neurodegenerative disease. Nature medicine 2004, 10 (7), S10. 16. Lanoiselée, H.-M.; Nicolas, G.; Wallon, D.; Rovelet-Lecrux, A.; Lacour, M.; Rousseau, S.; Richard, A.-C.; Pasquier, F.; Rollin-Sillaire, A.; Martinaud, O., APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS medicine 2017, 14 (3), e1002270. 17. Liu, C.-C.; Kanekiyo, T.; Xu, H.; Bu, G., Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nature Reviews Neurology 2013, 9 (2), 106. 18. Thomas, T.; Thomas, G.; McLendon, C.; Sutton, T.; Mullan, M., β-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 1996, 380 (6570), 168. 19. Mattson, M. P.; Lovell, M. A.; Furukawa, K.; Markesbery, W. R., Neurotrophic factors attenuate glutamate‐induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. Journal of neurochemistry 1995, 65 (4), 1740-1751. 20. Behl, C.; Davis, J.; Lesley, R.; Schubert, D., Hydrogen peroxide mediates amyloid β protein toxicity. Cell 1994, 77 (6), 817-827. 21. Christen, Y., Oxidative stress and Alzheimer disease. The American journal of clinical nutrition 2000, 71 (2), 621S-629S. 22. Markesbery, W. R., Oxidative stress hypothesis in Alzheimer's disease. Free Radical Biology and Medicine 1997, 23 (1), 134-147. 23. Resende, R.; Ferreiro, E.; Pereira, C.; De Oliveira, C. R., Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1-42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell death. Neuroscience 2008, 155 (3), 725-737. 24. Ahmed, M.; Davis, J.; Aucoin, D.; Sato, T.; Ahuja, S.; Aimoto, S.; Elliott, J. I.; Van Nostrand, W. E.; Smith, S. O., Structural conversion of neurotoxic amyloid-β 1–42 oligomers to fibrils. Nature structural & molecular biology 2010, 17 (5), 561. 25. Dahlgren, K. N.; Manelli, A. M.; Stine, W. B.; Baker, L. K.; Krafft, G. A.; LaDu, M. J., Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability. Journal of Biological Chemistry 2002. 26. Sakono, M.; Zako, T., Amyloid oligomers: formation and toxicity of Aβ oligomers. The FEBS journal 2010, 277 (6), 1348-1358. 27. Renner, M.; Lacor, P. N.; Velasco, P. T.; Xu, J.; Contractor, A.; Klein, W. L.; Triller, A., Deleterious effects of amyloid β oligomers acting as an extracellular scaffold for mGluR5. Neuron 2010, 66 (5), 739-754. 28. Spires-Jones, T. L.; Hyman, B. T., The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 2014, 82 (4), 756-771. 29. Solito, E.; Sastre, M., Microglia function in Alzheimer’s disease. Frontiers in pharmacology 2012, 3, 14. 30. Heneka, M. T.; Carson, M. J.; El Khoury, J.; Landreth, G. E.; Brosseron, F.; Feinstein, D. L.; Jacobs, A. H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R. M., Neuroinflammation in Alzheimer's disease. The Lancet Neurology 2015, 14 (4), 388-405. 31. Kim, A.; Lim, S.; Kim, Y., Metal ion effects on Aβ and tau aggregation. International journal of molecular sciences 2018, 19 (1), 128. 32. Faller, P.; Hureau, C.; Berthoumieu, O., Role of metal ions in the self-assembly of the Alzheimer’s amyloid-β peptide. Inorganic chemistry 2013, 52 (21), 12193-12206. 33. Tõugu, V.; Tiiman, A.; Palumaa, P., Interactions of Zn (II) and Cu (II) ions with Alzheimer's amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity. Metallomics 2011, 3 (3), 250-261. 34. Hane, F.; Leonenko, Z., Effect of metals on kinetic pathways of amyloid-β aggregation. Biomolecules 2014, 4 (1), 101-116. 35. Campbell, A., The role of aluminum and copper on neuroinflammation and Alzheimer's disease. Journal of Alzheimer's Disease 2006, 10 (2-3), 165-172. 36. Cheignon, C.; Tomas, M.; Bonnefont-Rousselot, D.; Faller, P.; Hureau, C.; Collin, F., Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology 2018, 14, 450-464. 37. Makena Ntimi, C. a. R., Rozita and Adam, Aishah and Nordin, An overview of in vitro research models for Alzheimer`s disease (AD). Regenerative Research, 2015, 2 (2), 8-13. 38. Jan, A.; Hartley, D. M.; Lashuel, H. A., Preparation and characterization of toxic Aβ aggregates for structural and functional studies in Alzheimer's disease research. Nature protocols 2010, 5 (6), 1186. 39. Elder, G. A.; Gama Sosa, M. A.; De Gasperi, R., Transgenic mouse models of Alzheimer's disease. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine: A Journal of Translational and Personalized Medicine 2010, 77 (1), 69-81. 40. Spires, T. L.; Hyman, B. T., Transgenic models of Alzheimer's disease: learning from animals. NeuroRx 2005, 2 (3), 423-437. 41. Platt, T. L.; Reeves, V. L.; Murphy, M. P., Transgenic models of Alzheimer's disease: better utilization of existing models through viral transgenesis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2013, 1832 (9), 1437-1448. 42. Ali, A. A.; Ahmed, H. I.; Abu-Elfotuh, K., Modeling stages mimic Alzheimer’s disease induced by different doses of aluminum in rats: focus on progression of the disease in response to time. of 2016, 11, 2. 43. Yang, F.; Lim, G. P.; Begum, A. N.; Ubeda, O. J.; Simmons, M. R.; Ambegaokar, S. S.; Chen, P. P.; Kayed, R.; Glabe, C. G.; Frautschy, S. A., Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Journal of Biological Chemistry 2005, 280 (7), 5892-5901. 44. Garcia‐Alloza, M.; Borrelli, L.; Rozkalne, A.; Hyman, B.; Bacskai, B., Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. Journal of neurochemistry 2007, 102 (4), 1095-1104. 45. Ye, J.; Zhang, Y., Curcumin protects against intracellular amyloid toxicity in rat primary neurons. International journal of clinical and experimental medicine 2012, 5 (1), 44. 46. Park, S.-Y.; Kim, H.-S.; Cho, E.-K.; Kwon, B.-Y.; Phark, S.; Hwang, K.-W.; Sul, D., Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Food and Chemical Toxicology 2008, 46 (8), 2881-2887. 47. Giri, R. K.; Rajagopal, V.; Kalra, V. K., Curcumin, the active constituent of turmeric, inhibits amyloid peptide‐induced cytochemokine gene expression and CCR5‐mediated chemotaxis of THP‐1 monocytes by modulating early growth response‐1 transcription factor. Journal of neurochemistry 2004, 91 (5), 1199-1210. 48. Shimmyo, Y.; Kihara, T.; Akaike, A.; Niidome, T.; Sugimoto, H., Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation. Neuroreport 2008, 19 (13), 1329-1333. 49. Lin, R.; Chen, X.; Li, W.; Han, Y.; Liu, P.; Pi, R., Exposure to metal ions regulates mRNA levels of APP and BACE1 in PC12 cells: blockage by curcumin. Neuroscience letters 2008, 440 (3), 344-347. 50. Begum, A. N.; Jones, M. R.; Lim, G. P.; Morihara, T.; Kim, P.; Heath, D. D.; Rock, C. L.; Pruitt, M. A.; Yang, F.; Hudspeth, B., Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. Journal of Pharmacology and Experimental Therapeutics 2008, 326 (1), 196-208. 51. Thapa, A.; Jett, S. D.; Chi, E. Y., Curcumin attenuates amyloid-β aggregate toxicity and modulates amyloid-β aggregation pathway. ACS chemical neuroscience 2015, 7 (1), 56-68. 52. Chang, Y.; Huang, W.-J.; Tien, L.-T.; Wang, S.-J., Ginsenosides Rg1 and Rb1 enhance glutamate release through activation of protein kinase A in rat cerebrocortical nerve terminals (synaptosomes). European journal of pharmacology 2008, 578 (1), 28-36. 53. Wang, Y.-H.; Du, G.-H., Ginsenoside Rg1 inhibits β-secretase activity in vitro and protects against Aβ-induced cytotoxicity in PC12 cells. Journal of Asian Natural Products Research 2009, 11 (7), 604-612. 54. Huang, T.; Fang, F.; Chen, L.; Zhu, Y.; Zhang, J.; Chen, X.; Shidu Yan, S., Ginsenoside Rg1 Attenuates Oligomeric Aβ1-42-Induced Mitochondrial Dysfunction. Current Alzheimer Research 2012, 9 (3), 388-395. 55. Gong, Y. S.; Zhang, J. T., Effect of 17-β-estradiol and ginsenoside Rg1 on reactive microglia induced by β-amyloid peptides. Journal of Asian natural products research 1999, 1 (3), 153-161. 56. Su, F.; Yuan, L.; Zhang, L.; Hu, S., Ginsenosides Rg1 and Re act as adjuvant via TLR4 signaling pathway. Vaccine 2012, 30 (27), 4106-4112. 57. Song, X.-Y.; Hu, J.-F.; Chu, S.-F.; Zhang, Z.; Xu, S.; Yuan, Y.-H.; Han, N.; Liu, Y.; Niu, F.; He, X., Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats. European journal of pharmacology 2013, 710 (1-3), 29-38. 58. Gong, L.; Li, S.-L.; Li, H.; Zhang, L., Ginsenoside Rg1 protects primary cultured rat hippocampal neurons from cell apoptosis induced by β-amyloid protein. Pharmaceutical biology 2011, 49 (5), 501-507. 59. Xu, P.-x.; Wang, S.-w.; Yu, X.-l.; Su, Y.-j.; Wang, T.; Zhou, W.-w.; Zhang, H.; Wang, Y.-j.; Liu, R.-t., Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation. Behavioural brain research 2014, 264, 173-180. 60. Jiménez-Aliaga, K.; Bermejo-Bescós, P.; Benedí, J.; Martín-Aragón, S., Quercetin and rutin exhibit antiamyloidogenic and fibril-disaggregating effects in vitro and potent antioxidant activity in APPswe cells. Life sciences 2011, 89 (25-26), 939-945. 61. Asai, M.; Iwata, N.; Yoshikawa, A.; Aizaki, Y.; Ishiura, S.; Saido, T. C.; Maruyama, K., Berberine alters the processing of Alzheimer’s amyloid precursor protein to decrease Aβ secretion. Biochemical and Biophysical Research Communications 2007, 352 (2), 498-502. 62. Zhu, F.; Wu, F.; Ma, Y.; Liu, G.; Li, Z.; Sun, Y. a.; Pei, Z., Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells. BMC neuroscience 2011, 12 (1), 125. 63. Lv, J.; Jia, H.; Jiang, Y.; Ruan, Y.; Liu, Z.; Yue, W.; Beyreuther, K.; Tu, P.; Zhang, D., Tenuifolin, an extract derived from tenuigenin, inhibits amyloid‐β secretion in vitro. Acta Physiologica 2009, 196 (4), 419-425. 64. R Howes, M.-J.; J Houghton, P., Ethnobotanical treatment strategies against Alzheimer's disease. Current Alzheimer Research 2012, 9 (1), 67-85. 65. Pages, N.; Maurois, P.; Delplanque, B.; Bac, P.; Stables, J. P.; Tamariz, J.; Chamorro, G.; Vamecq, J., Activities of α-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties. Neuroscience research 2010, 68 (4), 337-344. 66. Howes, M.-J. R.; Houghton, P. J., Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacology Biochemistry and Behavior 2003, 75 (3), 513-527. 67. Zhang, J.-S.; Zhou, S.-F.; Wang, Q.; Guo, J.-N.; Liang, H.-M.; Deng, J.-B.; He, W.-Y., Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/eIF2α pathway in Alzheimer’s disease. Neuroscience 2016, 325, 1-9. 68. Jang, J.-H.; Son, Y.; Kang, S. S.; Bae, C.-S.; Kim, J.-C.; Kim, S.-H.; Shin, T.; Moon, C., Neuropharmacological potential of Gastrodia elata Blume and its components. Evidence-Based Complementary and Alternative Medicine 2015, 2015. 69. Lin, Z.; Gu, J.; Xiu, J.; Mi, T.; Dong, J.; Tiwari, J. K., Traditional chinese medicine for senile dementia. Evidence-Based Complementary and Alternative Medicine 2012, 2012. 70. Zhang, X.; Zhang, A.; Jiang, B.; Bao, Y.; Wang, J.; An, L., Further pharmacological evidence of the neuroprotective effect of catalpol from Rehmannia glutinosa. Phytomedicine 2008, 15 (6-7), 484-490. 71. Howes, M.-J. R.; Perry, E., The role of phytochemicals in the treatment and prevention of dementia. Drugs & aging 2011, 28 (6), 439-468. 72. Wang, C.; Sun, J.; Luo, Y.; Xue, W.; Diao, H.; Dong, L.; Chen, J.; Zhang, J., A polysaccharide isolated from the medicinal herb Bletilla striata induces endothelial cells proliferation and vascular endothelial growth factor expression in vitro. Biotechnology letters 2006, 28 (8), 539-543. 73. Wang, Y.; Liu, D.; Chen, S.; Wang, Y.; Jiang, H.; Yin, H., A new glucomannan from Bletilla striata: structural and anti-fibrosis effects. Fitoterapia 2014, 92, 72-78. 74. Yue, L.; Wang, W.; Wang, Y.; Du, T.; Shen, W.; Tang, H.; Wang, Y.; Yin, H., Bletilla striata polysaccharide inhibits angiotensin II-induced ROS and inflammation via NOX4 and TLR2 pathways. International journal of biological macromolecules 2016, 89, 376-388. 75. Qu, Y.; Li, C.; Zhang, C.; Zeng, R.; Fu, C., Optimization of infrared-assisted extraction of Bletilla striata polysaccharides based on response surface methodology and their antioxidant activities. Carbohydrate polymers 2016, 148, 345-353. 76. Klunk, W. E.; Jacob, R. F.; Mason, R. P., Quantifying amyloid β-peptide (Aβ) aggregation using the Congo Red-Aβ (CR–Aβ) spectrophotometric assay. Analytical biochemistry 1999, 266 (1), 66-76. 77. Chong-sheng, B.; Fan, W.; Han-song, Z.; Yan-fei, L., Effects of subchronic aluminum exposure on liver function in rats. Journal of Northeast Agricultural University (English Edition) 2012, 19 (2), 62-65. 78. Giknis, M.; Clifford, C. B., Clinical laboratory parameters for Crl: WI (Han). Charles River Laboratories 2008. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72881 | - |
dc.description.abstract | 阿茲海默症為一種常見的神經退化疾病,是造成失智症的主要原因之一。類澱粉蛋白(Amyloid-β) 被視為造成阿茲海默症的起因之一,其由前類澱粉蛋白 (Amyloid precursor protein) 被 β-secretase 與 γ-secretase切割後所產生。當類澱粉蛋白聚集於大腦時,會造成氧化壓力 (oxidative stress)、慢性發炎反應 (chronic inflammatory response) 以及神經突觸功能喪失 (synaptic dysfunction),導致大腦神經退化與死亡,而目前臨床上尚未有能夠治療阿茲海默症的藥物。白芨多醣體已被證實具有的抗氧化、抗發炎與促進細胞增殖的特性,本研究希望能夠藉由白芨多醣體之特性降低類澱粉蛋白所造成的細胞毒性,並進一步探討白芨多醣體對 β-secretase 表現量之影響,以達到預防及治療阿茲海默症。
本研究以 FTIR 與 NMR 確認萃取出白芨多醣體的官能基與結構;透過ThT assay、Western Blot 與 TEM 觀察類澱粉蛋白纖維與寡聚醣的形成。體外實驗的部分,依據 ISO 10993 規範,由WST-1 測試確認其生物相容性;DCFDA 與 RT-PCR 確認抗氧化與抗發炎效果;Live and Dead 觀察白芨多醣體抑制類澱粉蛋白產生細胞毒性之能力。體內實驗部分,行為實驗水迷宮評估老鼠的記憶能力;Western Blot評估白芨多醣體抑制 β-secretase表現量之能力;組織切片染色呈現海馬迴與大腦皮質的細胞與組織之狀況;免疫組織化學染色觀察海馬迴與大腦皮質中類澱粉蛋白的多寡與分布。 根據目前的實驗結果,體外實驗中,我們已成功證實白芨多醣體能夠預防與治療類澱粉蛋白所誘發的氧化壓力與發炎反應,有效降低類澱粉蛋白所造成的細胞毒性。體內實驗中,我們已成功證實白芨多醣體能夠有效減緩氯化鋁誘導之阿茲海默症老鼠的症狀,藉由海馬迴與大腦皮質中的損壞,降低記憶能力的喪失,也藉由降低 β-secretase 的表現量,以減少類澱粉蛋白的產生與斑塊之堆疊。 | zh_TW |
dc.description.abstract | Alzheimer’s disease (AD) is the primary cause of age-related dementia. Amyloid-β (Aβ) is regarded as one of the reasons of AD. Amyloid precursor protein is cleaved by β-secretase and γ-secretase to produce amyloid-β, whose aggregation implicates in neuronal degeneration and cognitive decline in AD. It induces oxidative stress, chronic neuroinflammation, and synaptic dysfunction, leading to the death of neurons in the brain. Nowadays, there is no effective therapy to cure AD in clinical treatment. Bletilla Striata polysaccharide (BSP) has been proved to have anti-oxidative, anti-inflammatory effects and be able to induce cell proliferation. Therefore, the purpose of this study is to utilize the characteristics of BSP to reduce Aβ-induced cytotoxicity. Further, we explore the effect of BSP on β-secretase levels to achieve the prevention and treatment of AD.
In this study, FTIR and NMR are used to confirm the functional groups and chemical structure of BSP. ThT assay, Western blot and TEM are used to observe the formation of Aβ fibrils and oligomers. WST-1 assay is used to confirm the biocompatibility of BSP. DCFDA and RT-PCR tests are used to confirm the anti-oxidative and anti-inflammatory effects of BSP. Live and Dead test is used to verify the ability of BSP to reduce the cytotoxicity of Aβ. Morris Water Maze is performed to evaluate the retention of working and spatial memory in rats. Western Blot is used to evaluate the ability of BSP to decrease β-secretase levels. Section of cortex and hippocampus tissues are stained with hematoxylin and eosin to observe the cells and the tissues. Immunohistochemical staining of the section of cortex and hippocampus tissues is used to show the distribution of amyloid-β. The blood test is used to evaluate the biochemistry of blood. The current results had successfully proven that BSP could reduce the cytotoxicity of amyloid-β through the treatment and prevention of the oxidative stress and inflammation induced by amyloid-β. Furthermore, reducing in the damage of hippocampus and cortex lead to attenuate the neurobehavioral impairments by treating BSP in AlCl3-induced Alzheimeric rats. Meanwhile, the evidence of greatly reducing in β-secretase levels and the deposit of amyloid-β plaque were found in the BSP treated rats. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:09:04Z (GMT). No. of bitstreams: 1 ntu-108-R06548010-1.pdf: 5072402 bytes, checksum: a175abd2d8b4a54fef8c8d091c8c4fb5 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 致謝 ......I
中文摘要 ......II Abstract ......III 目錄 ......IV 圖目錄 ......VII 表目錄 ......X 縮寫目錄 ......XI 公式目錄 ......XIII 第一章 緒論 ......1 1.1 前言 ...... 1.2 阿茲海默症簡介 ......1 1.3 治療方法與臨床試驗 ......1 1.4 研究目的 ......2 第二章 文獻回顧 ......3 2.1 阿茲海默症假說 ......3 2.1.1 膽鹼能假說 ......3 2.1.2 濤蛋白假說 ......3 2.1.3 類澱粉蛋白假說 ......4 2.2 金屬離子對阿茲海默症之影響 ......7 2.3 阿茲海默症體外模型 ......9 2.3.1 類神經元細胞體外模型建立 ......9 2.3.2 類澱粉蛋白體外模型建立 ......9 2.4 阿茲海默症體內模型 ......10 2.5 類澱粉蛋白學說治療策略發展 ......11 2.6 白芨與白芨多醣體 ......17 第三章 實驗方法 ......18 3.1 實驗藥品 ......18 3.2 實驗儀器 ......19 3.3 實驗架構 ......20 3.4 材料製備與分析 ......21 3.4.1 白芨多醣體 ......21 3.4.2 類澱粉蛋白模型製備前處理 ......22 3.4.3 類澱粉蛋白寡聚醣模型 ......22 3.4.4 類澱粉蛋白纖維模型 ......22 3.5 In vitro 體外實驗 ......23 3.5.1 細胞株培養 ......23 3.5.2 WST-1 生物相容性測試 ......23 3.5.3 DCFDA - ROS測試 ......24 3.5.4 RT-PCR - 抗發炎測試 ......24 3.5.5 Live and Dead細胞活性測試 ......24 3.6 In vivo 體內實驗 ......27 3.6.1 AlCl3誘發阿茲海默症老鼠 ......27 3.6.2 行為實驗 – 水迷宮 (Water Maze) ......27 3.6.3 Western Blot – β-secretase ......28 3.6.4 組織切片染色 (H&E Staining) ......29 3.6.5 免疫組織化學染色 (Immunohistochemistry) ......29 3.6.6 血液檢測 (Blood Test) ......30 3.7 統計分析 ......30 第四章 結果與討論 ......31 4.1 白芨多醣體 (BSP) 之材料分析 ......31 4.1.1 傅立葉轉換紅外線 (FTIR) ......31 4.1.2 核磁共振光譜 (NMR) ......32 4.2 類澱粉蛋白模型建立 ......34 4.3 In vitro 體外實驗 ......37 4.3.1 WST-1 生物相容性測試 ......37 4.3.2 DCFDA – ROS 測試 ......37 4.3.3 RT-PCR – 抗發炎測試 ......39 4.3.4 Live and Dead 細胞活性 ......43 4.4 In vivo 體內實驗 ......46 4.4.1 行為實驗-水迷宮 (Water Maze) ......46 4.4.2 Western Blot - β-secretase ......48 4.4.3 組織切片染色 (H&E Staining) ......49 4.4.4 免疫組織化學染色 (Immunohistochemistry) ......50 4.4.5 血液檢測 ......51 第五章 結論 ......52 參考文獻 ......53 | |
dc.language.iso | zh-TW | |
dc.title | 探討白芨多醣體降低類澱粉蛋白之細胞毒性及其在預防及治療阿茲海默症之效果 | zh_TW |
dc.title | The Effect of Bletilla Striata Polysaccharide on Reducing Aβ-induced Cytotoxicity for Alzheimer's Disease Prevention and Therapy | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳造中,郭士民 | |
dc.subject.keyword | 阿茲海默症,類澱粉蛋白,白芨,白芨多醣體,β-secretase, | zh_TW |
dc.subject.keyword | Alzheimer’s disease,Amyloid-β,Bletilla Striata,Bletilla Striata polysaccharide,β-secretase, | en |
dc.relation.page | 62 | |
dc.identifier.doi | 10.6342/NTU201901622 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-07-23 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
顯示於系所單位: | 醫學工程學研究所 |
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