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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46617完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳玉怜(Yuh-Lien Chen) | |
| dc.contributor.author | Wen-Yu Weng | en |
| dc.contributor.author | 翁郁雯 | zh_TW |
| dc.date.accessioned | 2021-06-15T05:19:02Z | - |
| dc.date.available | 2013-09-09 | |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-20 | |
| dc.identifier.citation | Bao, X., Liu, C., Fang, J., and Li, X. (2001). Structural and immunological studies of a major polysaccharide from spores of Ganoderma lucidum (Fr.) Karst. Carbohydr Res 332, 67-74.
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Ganodermataceae: natural products and their related pharmacological functions. Am J Chin Med 35, 559-574. 林佳穎. (2008).靈芝多醣體對內毒素處理小鼠及人類主動脈平滑肌細胞之介白素-1表現的影響及其機轉.國立台灣大學解剖學暨細胞生物學研究所. 楊令仰. (2001). 靈芝對小鼠動脈粥狀硬化與乙醯氨酚引發肝損傷之保護作用.國立陽明大學藥理學研究所 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46617 | - |
| dc.description.abstract | 在動脈硬化與血管再狹窄的過程中，原來位在血管中層的平滑肌細胞(smooth muscle cells)會移行到內皮細胞下空間 (subendothelial space)，並在這個區域進行大量增生，造成內膜增厚 (intimal hyperplasia)的主要因素。同時血管再狹窄及動脈硬化發生的原因也和血管發炎密切有關，因此找到具有抗發炎及抑制血管平滑肌細胞增生的藥物對於治療血管疾病會有很大的幫助。靈芝多醣體 (Extract of Ganoderma lucidum polysaccharides, EORP)除了具有調節免疫力、抑制腫瘤細胞增生的功效外，我們實驗室在先前的研究也發現它有抑制血管平滑肌細胞發炎的作用，然而靈芝多醣體對血管平滑肌細胞增生的影響及相關機轉仍未清楚。本實驗主要探討靈芝多醣體對PDGF (platelet-derived growth factor)處理人類主動脈平滑肌細胞和小鼠血管內膜增生的影響。首先利用細胞計數法、MTT (3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay及5-bromodeoxyuridine (BrdU) incorporation實驗證實EORP會抑制PDGF刺激人類主動脈平滑肌細胞的增生。接著以流式細胞儀實驗發現EORP會增加在G0/G1期的細胞比例並降低S期細胞比例，達到抑制細胞週期的進行，然後以西方墨點法實驗證實EORP可以降低人類主動脈平滑肌細胞受PDGF刺激後，其Cyclin D1、Cyclin E、CDK2 (Cyclin-dependent kinase 2)的表現及增加p27的表現。另外，EORP會抑制PDGF刺激人類主動脈平滑肌細胞JNK/SAPK (stress-activated protein kinase)及p38的磷酸化。進一步經由BrdU incorporation實驗，以mitogen-activated protein kinases (MAPKs) inhibitor與EORP共同處理證明EORP是透過抑制JNK磷酸化影響PDGF刺激人類主動脈平滑肌細胞增生。動物實驗方面，利用血管去內皮手術建立血管再狹窄、內膜增厚的動物模式，以EORP餵食手術後小鼠兩週，發現EORP有效抑制小鼠血管內膜增生與降低細胞增生標記蛋白PCNA (proliferating cell nuclear antigen)的表現。綜合上述實驗結果得知EORP對於PDGF引起人類主動脈平滑肌細胞的增生作用是個有效的抑制劑，而且以EORP餵食也可以降低去內皮手術後小鼠血管內膜增生的形成，顯示EORP對動脈硬化或血管再狹窄的預防或治療有很大的助益。 | zh_TW |
| dc.description.abstract | Vascular smooth muscle cell (VSMCs) proliferation, triggered by inflammatory response of the vascular wall, is considered to be the key event in the development of atherosclerosis and restenosis. Therefore, the identification of novel compounds with combined anti-inflammatory and anti-proliferative properties may be an attractive therapeutic strategy for the prevention of cardiovascular diseases. A glucan-containing extract of Ganoderma lucidum-derived polysaccharides (EORP) has been proposed to possess immuno-modulatory functions and antitumor activities. However, its effects on the proliferation of VSMCs and the relative mechanisms remain unclear. In this study we aimed to examine the effects of EORP on the PDGF (platelet-derived growth factor)-treated human aortic smooth muscle cells (HASMCs) and neointimal hyperplasia in endothelia-denuded femoral artery of mice. EORP treatment inhibited proliferation of PDGF-treated HASMCs demonstrated by cell count, MTT (3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and 5-bromodeoxyuridine (BrdU) incorporation (MTT data, control:1; PDGF:1.38±0.01; PDGF+10 μg/mL EORP:1.03±0.02; cell count data, control:15.45±0.65×103; PDGF:23.25±0.05×103; BrdU data: control: 0.02±0.01; PDGF: 0.08±0.01; PDGF+10 μg/mL EORP: 0.02±0.00). Flow cytometry analysis showed EORP altered cell cycle distribution. EORP decreased cell proportion of S phase and increased cell proportion of G0/G1 phase (G0/G1 phase, contol:89.1±1.4 %; PDGF: 80.4±4.3 %, PDGF+10 μg/mL EORP: 85.7±3.8 %; S phase, control:1.7±0.9 %; PDGF: 5.8±2.8 %, PDGF+10 μg/mL EORP: 3.4±2.5 %). Western blot analysis demonstrated EORP downregulated PDGF-induced cyclin D1, cyclin E, CDK2 expression and upregulated p27 expression. Phosphorylation studies of MAPKs demonstrated that EORP suppressed PDGF-induced JNK/SAPK (stress-activated protein kinase) and p38 phosphorylation. For in vivo studies, oral EORP treatment reduces neointimal hyperplasia in endothelia-denuded femoral artery of mice (I/M ratio, endothelial denudation: 1.46±0.30; EORP+endothelial denudation: 0.67±0.03) and downregulated cell proliferation marker-PCNA (proliferating cell nuclear antigen) expression (PCNA positive cells ratio, endothelial denudation: 79.44±3.80 %; EORP+endothelial denudation: 60.78±2.65%). These results suggest that EORP may provide an effective novel approach to prevent vascular diseases through inhibition of vascular smooth muscle cells proliferation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T05:19:02Z (GMT). No. of bitstreams: 1 ntu-99-R97446002-1.pdf: 1559921 bytes, checksum: 88a74e29438be6e61de7b1a36989bc83 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 中文摘要----------------------------------------------------------------------------------------Ⅰ
英文摘要----------------------------------------------------------------------------------------Ⅲ 壹、 緒論--------------------------------------------------------------------------------------1 一、 動脈硬化 (atherosclerosis)與血管再狹窄 (restenosis)-----------------1 二、 血管平滑肌細胞與動脈硬化及血管再狹窄之關係-----------------------2 三、 血小板衍生性生長因子(PDGF)與血管平滑肌細胞之關係------------3 四、 細胞增生與細胞週期之關係--------------------------------------------------4 五、 細胞增生和MAPKs的關係--------------------------------------------------5 六、 Ganoderma lucidum(靈芝)之藥理性質與應用----------------------------6 七、 研究動機--------------------------------------------------------------------------8 貳、 實驗材料--------------------------------------------------------------------------------9 參、 實驗方法-------------------------------------------------------------------------------14 肆、 實驗結果-------------------------------------------------------------------------------21 伍、 討論與結論----------------------------------------------------------------------------27 陸、 參考文獻-----------------------------------------------------------------------------31 柒、 附圖-------------------------------------------------------------------------------42 | |
| dc.language.iso | zh-TW | |
| dc.subject | 細胞週期 | zh_TW |
| dc.subject | 人類主動脈平滑肌細胞 | zh_TW |
| dc.subject | 血小板衍生性生長因子 | zh_TW |
| dc.subject | 動脈硬化 | zh_TW |
| dc.subject | 血管再狹窄 | zh_TW |
| dc.subject | human aortic smooth muscle cells | en |
| dc.subject | cell cycle | en |
| dc.subject | restenosis | en |
| dc.subject | atherosclerosis | en |
| dc.subject | PDGF | en |
| dc.title | 探討靈芝多醣體對PDGF處理血管平滑肌細胞和小鼠血管內膜增生的影響 | zh_TW |
| dc.title | The Effects of Ganoderma lucidum Polysaccharides on the Proliferation of Cultured Human Aortic Smooth Muscle Cells and the Neointimal Hyperplasia of Mice | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王淑美,吳建春,陳永祥,江美治 | |
| dc.subject.keyword | 人類主動脈平滑肌細胞,血小板衍生性生長因子,動脈硬化,血管再狹窄,細胞週期, | zh_TW |
| dc.subject.keyword | human aortic smooth muscle cells,PDGF,atherosclerosis,restenosis,cell cycle, | en |
| dc.relation.page | 53 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-07-21 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨生物細胞學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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