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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78476完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林君榮(Chun-Jung Lin) | |
| dc.contributor.author | Po-Hsuan Lai | en |
| dc.contributor.author | 賴柏軒 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:59:06Z | - |
| dc.date.available | 2025-03-13 | |
| dc.date.copyright | 2020-03-13 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-12-25 | |
| dc.identifier.citation | Alzheimer’s Association. 2018 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2018;14:367-429.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78476 | - |
| dc.description.abstract | 類風溼性關節炎是一種自體免疫疾病，該疾病最大特徵為關節發炎、軟骨損傷以及系統性發炎，此疾病帶來的系統性發炎可能導致神經發炎等影響，進而和神經退化性疾病的產生有所關連。本篇研究利用膠原蛋白誘發關節炎大鼠動物模型來探討類風濕性關節炎對於神經發炎、血腦屏障的影響，結果指出，除了細胞激素在腦部的上升外，類風溼性關節炎還可能造成微膠細胞和星狀細胞的活化。在血腦屏障方面，可觀察到其通透性上升以及ZO-1、Occludin表現量的下降，除了血腦屏障完整性之外，與-類澱粉蛋白在血腦屏障的運輸相關蛋白的表現也受到該疾病影響，其中RAGE、P-gp在腦部血管的表現量皆顯著上升，同時也觀察到β-類澱粉蛋白較容易從周邊進入海馬迴區域，近一步探討β-類澱粉蛋白在腦部外的清除機制後，更發現血中的可溶性Lrp-1和肝臟的P-gp表現量有所下降。綜上所述，類風溼性關節炎可導致神經發炎以及血腦屏障的功能失調，並可能導致-類澱粉蛋白在中樞運輸及周邊清除上的變化，這些影響可能進一步與神經退化疾病或阿茲海默失智症的發生有關。 | zh_TW |
| dc.description.abstract | Rheumatoid arthritis (RA) is an autoimmune disease, characterized by synovial inflammation, cartilage damage, and systemic inflammation. The systemic inflammation in RA can be associated with the occurrence of neuroinflammation and neurodegenerative diseases, like Alzheimer's disease (AD). In this study, the impacts of RA on neuroinflammation and the blood-brain barrier (BBB) were investigated in collagen induced arthritis (CIA) rats, an animal model exhibiting similar clinical features of human RA. As a result, along with an elevation of brain cytokine levels, the immunofluorescence analysis showed that both microglia activation and astrogliosis were increased in the brain of CIA rats. In terms of BBB function, the BBB permeability of sodium fluorescein, a marker compound for BBB integrity, was significantly increased in CIA rats. Moreover, the expression of tight junction proteins, Zona-occludin 1 and occludin, also decreased in brain capillaries of CIA rats. In addition to the change in BBB integrity, it is noted that the protein expression of the receptor of advanced glycation end product (RAGE) and P-glycoprotein (P-gp), both are important proteins for BBB transport of amyloid beta (Aβ), was significantly increased in brain capillaries of CIA rats. For brain transport of Aβ, hippocampus in CIA rats showed higher levels of Aβ influx from peripheral blood significantly. In addition to the change at the BBB, the levels of plasma sLrp-1 and hepatic P-gp were decreased, of which both are important for peripheral clearance of Aβ. In conclusion, significant neuroinflammation and BBB breakdown were observed in CIA rats, suggesting the link between RA and neurodegenerative disease. The increase of P-gp and RAGE at BBB along with the change in peripheral sLrp-1 and P-gp in CIA rats suggest that deposition of Aβ is altered in RA, which may be implicated in amyloid pathogenesis of neurodegenerative diseases or AD. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:59:06Z (GMT). No. of bitstreams: 1 ntu-108-R06423009-1.pdf: 2175004 bytes, checksum: 6e7dc49da8417fd76353a5bd78a6147d (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | TABLE OF CONTENTS
口試委員會審定書 # 誌謝 i 中文摘要 ii ABSTRACT iii CONTENTS iv LIST OF FIGURES vii Chapter 1 Introduction 1 1.1 Rheumatoid arthritis (RA) 1 1.2 BBB dysfunction 1 1.3 Alzheimer’s disease (AD) and amyloid beta (Aβ) 3 1.4 Clearance of amyloid beta (Aβ) 4 Chapter 2 Objective 10 Chapter 3 Materials and methods 11 3.1 Establishment of collagen induced arthritis (CIA) model in rat 11 3.2 Quantification of IL-1β, IL-6, and TNF-α in plasma 12 3.3 RNA extraction 13 3.3.1 Extraction RNA from brain tissue 13 3.3.2 Quality control 13 3.4 Reverse transcription-quantitative polymerase chain reaction, RT-qPCR 14 3.4.1 Reverse transcription (RT) 14 3.4.2 Real time-quantitative polymerase chain reaction (RT-qPCR) 15 3.5 Perfusion fixation of the rat brain 16 3.6 Immunofluorescence 16 3.7 BBB permeability 18 3.7.1 Administration of sodium fluorescein 18 3.7.2 Extraction of sodium fluorescein 18 3.8 Isolation of brain microvessels for Western blot analysis 19 3.9 Preparation of protein samples for immunoblot 19 3.9.1 Extraction of BMVs proteins 19 3.9.2 The isolation of membrane fraction from the liver 20 3.9.3 Extraction of tissue protein 20 3.10 Western blot 20 3.10.1 Quantification of protein concentration 20 3.10.2 Western blot 21 3.11 Kinetic of human amyloid beta 1-42 (Aβ42) in the plasma 22 3.11.1 Monomerization of human Aβ42 22 3.11.2 Intravenous administration of human Aβ42 22 3.11.3 Quantification of human Aβ42 in the plasma 23 3.12 Brain influx of human amyloid beta 1-42(Aβ42)24 3.12.1 Extraction of Aβ42 in the brain 24 3.12.2 Quantification of Aβ42 in the brain 25 3.13 Quantification of rat soluble LRP-1 in the plasma 25 3.14 Statistical analysis 26 Chapter 4 Results 29 4.1 Evaluation of collagen-induced arthritis (CIA) animal model in rats 29 4.2 Neuroinflammation in CIA rats 29 4.3 BBB dysfunction in CIA rats 30 4.4 The change in the expression of amyloid beta (Aβ) related carriers at brain capillaries in CIA rats 30 4.5 Brain influx of amyloid beta (Aβ) in CIA rats 31 4.6 Peripheral clearance of amyloid beta (Aβ) in CIA rats 32 Chapter 5 Discussion 42 Chapter 6 Conclusion 48 References 49 LIST OF FIGURES Figure 1.1 Blood brain barrier (BBB) 6 Figure 1.2 Generation and oligomerization of Aβ 7 Figure 1.3 Sequences of amyloid beta (Aβ) 1-40 and 42 8 Figure 1.4 Clearance of amyloid beta (Aβ) in the CNS and BBB 8 Figure 1.5 Elimination of amyloid beta (Aβ) in the peripheral system 9 Figure 3.1 Establishment of saline injected control and collagen-induced arthritis (CIA) in Lewis female rats 27 Figure 3.2 Flow charts of brain microvessels (BMVs) isolation 28 Figure 4.1 Evaluation of collagen-induced arthritis (CIA) animal model in rats 33 Figure 4.2 Fold change in the mRNA expression of pro-inflammatory cytokines 34 Figure 4.3 Microglia and astrocyte activation 35 Figure 4.4 BBB permeability and the expression of tight junction proteins 36 Figure 4.5 Expression of amyloid beta (Aβ) related carriers 37 Figure 4.6 Immunofluorescence of P-gp and RAGE in the brain 38 Figure 4.7 Immunoblots of pre-disaggregate human amyloid beta 42 (Aβ42) 39 Figure 4.8 Brain influx of peripheral human amyloid beta 1-42 (Aβ42) 40 Figure 4.9 Clearance of amyloid beta 1-42 (Aβ42) in peripheral 41 | |
| dc.language.iso | en | |
| dc.subject | 血腦屏障 | zh_TW |
| dc.subject | 類澱粉蛋白 | zh_TW |
| dc.subject | 神經發炎 | zh_TW |
| dc.subject | 阿茲海默症 | zh_TW |
| dc.subject | 類風溼性關節炎 | zh_TW |
| dc.subject | amyloid beta | en |
| dc.subject | neuroinflammation | en |
| dc.subject | BBB | en |
| dc.subject | rheumatoid arthritis | en |
| dc.title | 類風溼性關節炎對於神經發炎以及血腦屏障類澱粉蛋白之運輸在大鼠中之影響之探討 | zh_TW |
| dc.title | The effect of rheumatoid arthritis on neuroinflammation and blood-brain barrier transportation of amyloid beta in rats | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳儀莊(Yi-Juang Chern),孔繁璐,姚宗珍 | |
| dc.subject.keyword | 類風溼性關節炎,阿茲海默症,類澱粉蛋白,神經發炎,血腦屏障, | zh_TW |
| dc.subject.keyword | rheumatoid arthritis,amyloid beta,neuroinflammation,BBB, | en |
| dc.relation.page | 57 | |
| dc.identifier.doi | 10.6342/NTU201904424 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-12-25 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-03-13 | - |
| 顯示於系所單位： | 藥學系 | |
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