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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76668完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王淑慧(Shu-Huei Wang) | |
| dc.contributor.author | Pin-Yu Chen | en |
| dc.contributor.author | 陳品聿 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:34:47Z | - |
| dc.date.available | 2021-07-10T21:34:47Z | - |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-19 | |
| dc.identifier.citation | 1. Li, X., et al., Atherosclerotic coronary artery disease: The accuracy of measures to diagnose preclinical atherosclerosis. Exp Ther Med, 2016. 12(5): p. 2899-2902. 2. Benjamin, E.J., et al., Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation, 2019. 139(10): p. e56-e528. 3. Scott, N.A., Restenosis following implantation of bare metal coronary stents: pathophysiology and pathways involved in the vascular response to injury. Adv Drug Deliv Rev, 2006. 58(3): p. 358-76. 4. Anderson, H.V., et al., A contemporary overview of percutaneous coronary interventions. The American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR). J Am Coll Cardiol, 2002. 39(7): p. 1096-103. 5. Bazzoni, G. and E. Dejana, Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev, 2004. 84(3): p. 869-901. 6. Andersson, K.E. and K. Persson, The L-arginine/nitric oxide pathway and non-adrenergic, non-cholinergic relaxation of the lower urinary tract. Gen Pharmacol, 1993. 24(4): p. 833-9. 7. Tabas, I., Pulling down the plug on atherosclerosis: finding the culprit in your heart. Nat Med, 2011. 17(7): p. 791-3. 8. Anderson, T.J., Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol, 1999. 34(3): p. 631-8. 9. Funk, S.D., A. Yurdagul, Jr., and A.W. Orr, Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int J Vasc Med, 2012. 2012: p. 569654. 10. Yang, X., et al., Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies. Front Physiol, 2017. 8: p. 600. 11. Zmyslowski, A. and A. Szterk, Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols. Lipids Health Dis, 2017. 16(1): p. 188. 12. Ma, S., et al., E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Sci Rep, 2016. 6: p. 22910. 13. Nakashima, Y., et al., Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol, 1998. 18(5): p. 842-51. 14. Libby, P., P.M. Ridker, and A. Maseri, Inflammation and atherosclerosis. Circulation, 2002. 105(9): p. 1135-43. 15. Seo, J.W., et al., Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein. Mediators Inflamm, 2015. 2015: p. 235797. 16. Strauss, B.H., et al., Extracellular-Matrix Remodeling after Balloon Angioplasty Injury in a Rabbit Model of Restenosis. Circulation Research, 1994. 75(4): p. 650-658. 17. Ross, R., et al., Localization of Pdgf-B Protein in Macrophages in All Phases of Atherogenesis. Science, 1990. 248(4958): p. 1009-1012. 18. Katakami, N., Mechanism of Development of Atherosclerosis and Cardiovascular Disease in Diabetes Mellitus. J Atheroscler Thromb, 2018. 25(1): p. 27-39. 19. Handa, N., et al., Ischemic stroke events and carotid atherosclerosis. Results of the Osaka Follow-up Study for Ultrasonographic Assessment of Carotid Atherosclerosis (the OSACA Study). Stroke, 1995. 26(10): p. 1781-6. 20. Pedersen, T.R., et al., Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. Atheroscler Suppl, 2004. 5(3): p. 81-7. 21. Gruntzig, A., Transluminal dilatation of coronary-artery stenosis. Lancet, 1978. 1(8058): p. 263. 22. Holmes, D.R., Jr., et al., Restenosis after percutaneous transluminal coronary angioplasty (PTCA): a report from the PTCA Registry of the National Heart, Lung, and Blood Institute. Am J Cardiol, 1984. 53(12): p. 77C-81C. 23. Fischman, D.L., et al., A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med, 1994. 331(8): p. 496-501. 24. Wilensky, R.L., et al., Vascular injury, repair, and restenosis after percutaneous transluminal angioplasty in the atherosclerotic rabbit. Circulation, 1995. 92(10): p. 2995-3005. 25. Miller, A.M., et al., Inhibition by leukocyte depletion of neointima formation after balloon angioplasty in a rabbit model of restenosis. Cardiovasc Res, 2001. 49(4): p. 838-50. 26. Fingerle, J., et al., Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci U S A, 1989. 86(21): p. 8412-6. 27. Liu, M.W., G.S. Roubin, and S.B. King, 3rd, Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia. Circulation, 1989. 79(6): p. 1374-87. 28. Zohlnhofer, D., et al., Gene expression profiling of human stent-induced neointima by cDNA array analysis of microscopic specimens retrieved by helix cutter atherectomy: Detection of FK506-binding protein 12 upregulation. Circulation, 2001. 103(10): p. 1396-402. 29. Bochaton-Piallat, M.L., et al., Phenotypic heterogeneity of rat arterial smooth muscle cell clones. Implications for the development of experimental intimal thickening. Arterioscler Thromb Vasc Biol, 1996. 16(6): p. 815-20. 30. Thyberg, J., et al., Phenotypic modulation of smooth muscle cells after arterial injury is associated with changes in the distribution of laminin and fibronectin. J Histochem Cytochem, 1997. 45(6): p. 837-46. 31. Boehm, M. and E.G. Nabel, Cell cycle and cell migration: new pieces to the puzzle. Circulation, 2001. 103(24): p. 2879-81. 32. Nabel, E.G., CDKs and CKIs: molecular targets for tissue remodelling. Nat Rev Drug Discov, 2002. 1(8): p. 587-98. 33. Tanner, F.C., et al., Expression of cyclin-dependent kinase inhibitors in vascular disease. Circ Res, 1998. 82(3): p. 396-403. 34. Vidal, A. and A. Koff, Cell-cycle inhibitors: three families united by a common cause. Gene, 2000. 247(1-2): p. 1-15. 35. Sherr, C.J. and J.M. Roberts, Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev, 1995. 9(10): p. 1149-63. 36. Innocenti, M., New insights into the formation and the function of lamellipodia and ruffles in mesenchymal cell migration. Cell Adh Migr, 2018. 12(5): p. 401-416. 37. Dmitrieff, S. and F. Nedelec, Amplification of actin polymerization forces. J Cell Biol, 2016. 212(7): p. 763-6. 38. Friedl, P. and K. Wolf, Plasticity of cell migration: a multiscale tuning model. J Cell Biol, 2010. 188(1): p. 11-9. 39. Schillinger, M. and E. Minar, Restenosis after percutaneous angioplasty: the role of vascular inflammation. Vasc Health Risk Manag, 2005. 1(1): p. 73-8. 40. Serrano, C.V., Jr., et al., Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression. Evidence of inflammatory responses in coronary angioplasty. J Am Coll Cardiol, 1997. 29(6): p. 1276-83. 41. Belch, J.J., et al., The white blood cell adhesion molecule E-selectin predicts restenosis in patients with intermittent claudication undergoing percutaneous transluminal angioplasty. Circulation, 1997. 95(8): p. 2027-31. 42. Kamijikkoku, S., et al., Acute myocardial infarction and increased soluble intercellular adhesion molecule-1: a marker of vascular inflammation and a risk of early restenosis? Am Heart J, 1998. 136(2): p. 231-6. 43. Wilcox, J.N., et al., Perivascular responses after angioplasty which may contribute to postangioplasty restenosis: a role for circulating myofibroblast precursors? Ann N Y Acad Sci, 2001. 947: p. 68-90; dicussion 90-2. 44. Manning, B.D. and L.C. Cantley, AKT/PKB signaling: navigating downstream. Cell, 2007. 129(7): p. 1261-74. 45. Kim, J.Y., et al., Apamin inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration through suppressions of activated Akt and Erk signaling pathway. Vascul Pharmacol, 2015. 70: p. 8-14. 46. Yan, L.J., et al., Cordycepin inhibits vascular adhesion molecule expression in TNF-alpha-stimulated vascular muscle cells. Exp Ther Med, 2017. 14(3): p. 2335-2340. 47. Yang, G., et al., A Positive Feedback Loop between Akt and mTORC2 via SIN1 Phosphorylation. Cell Rep, 2015. 12(6): p. 937-43. 48. Kipshidze, N., et al., Role of the endothelium in modulating neointimal formation: vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions. J Am Coll Cardiol, 2004. 44(4): p. 733-9. 49. Asahara, T., et al., Isolation of putative progenitor endothelial cells for angiogenesis. Science, 1997. 275(5302): p. 964-7. 50. Hill, J.M., et al., Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med, 2003. 348(7): p. 593-600. 51. Hristov, M., W. Erl, and P.C. Weber, Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol, 2003. 23(7): p. 1185-9. 52. Walter, D.H., et al., Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation, 2002. 105(25): p. 3017-24. 53. Blindt, R., et al., A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells. J Am Coll Cardiol, 2006. 47(9): p. 1786-95. 54. Park, B.Y., et al., Daphnane diterpene esters isolated from flower buds of Daphne genkwa induce apoptosis in human myelocytic HL-60 cells and suppress tumor growth in Lewis lung carcinoma (LLC)-inoculated mouse model. J Ethnopharmacol, 2007. 111(3): p. 496-503. 55. Lee, M.Y., et al., Anti-inflammatory activity of (-)-aptosimon isolated from Daphne genkwa in RAW264.7 cells. Int Immunopharmacol, 2009. 9(7-8): p. 878-85. 56. Kai, H., et al., [Pharmacological effects of Daphne genkwa and Chinese medical prescription, 'Jyu-So-To']. Yakugaku Zasshi, 2004. 124(6): p. 349-54. 57. Park, B.Y., et al., Isolation of flavonoids, a biscoumarin and an amide from the flower buds of Daphne genkwa and the evaluation of their anti-complement activity. Phytother Res, 2006. 20(7): p. 610-3. 58. Zhang, C.F., et al., Antioxidant effects of Genkwa flos flavonoids on Freunds adjuvant-induced rheumatoid arthritis in rats. J Ethnopharmacol, 2014. 153(3): p. 793-800. 59. Li, N., et al., Comparative evaluation of cytotoxicity and antioxidative activity of 20 flavonoids. J Agric Food Chem, 2008. 56(10): p. 3876-83. 60. Du, W.J., et al., Antitumor Activity of Total Flavonoids from Daphne genkwa in Colorectal Cancer. Phytother Res, 2016. 30(2): p. 323-30. 61. Wang, Y., et al., Synergistic anti-glioma effect of Hydroxygenkwanin and Apigenin in vitro. Chem Biol Interact, 2013. 206(2): p. 346-55. 62. Huang, Y.C., et al., Anticancer Effect and Mechanism of Hydroxygenkwanin in Oral Squamous Cell Carcinoma. Front Oncol, 2019. 9: p. 911. 63. Chou, L.F., et al., Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression. Biomolecules, 2019. 10(1). 64. Hong, J.Y., et al., Growth inhibition of human lung cancer cells via down-regulation of epidermal growth factor receptor signaling by yuanhuadine, a daphnane diterpene from Daphne genkwa. J Nat Prod, 2011. 74(10): p. 2102-8. 65. Kang, J.I., et al., Anti-Tumor Activity of Yuanhuacine by Regulating AMPK/mTOR Signaling Pathway and Actin Cytoskeleton Organization in Non-Small Cell Lung Cancer Cells. PLoS One, 2015. 10(12): p. e0144368. 66. Testa, J.R. and P.N. Tsichlis, AKT signaling in normal and malignant cells. Oncogene, 2005. 24(50): p. 7391-3. 67. Gao, S., et al., Salusin-alpha Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling. Cell Physiol Biochem, 2018. 50(5): p. 1740-1753. 68. Cheng, C., et al., PDGF-induced migration of vascular smooth muscle cells is inhibited by heme oxygenase-1 via VEGFR2 upregulation and subsequent assembly of inactive VEGFR2/PDGFRbeta heterodimers. Arterioscler Thromb Vasc Biol, 2012. 32(5): p. 1289-98. 69. Yang, D., et al., Proliferation of vascular smooth muscle cells under inflammation is regulated by NF-kappaB p65/microRNA-17/RB pathway activation. Int J Mol Med, 2018. 41(1): p. 43-50. 70. Choi, K.W., et al., Inhibition of TNF-alpha-induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via downregulation of the MAPK, Akt and NF-kappaB signaling pathways. Vascul Pharmacol, 2010. 53(5-6): p. 273-80. 71. Zhang, L., et al., Inhibition of PDGF-BB-induced proliferation and migration in VSMCs by proanthocyanidin A2: Involvement of KDR and Jak-2/STAT-3/cPLA2 signaling pathways. Biomed Pharmacother, 2018. 98: p. 847-855. 72. Lee, K., et al., Inhibition of VCAM-1 expression on mouse vascular smooth muscle cells by lobastin via downregulation of p38, ERK 1/2 and NF-kappaB signaling pathways. Arch Pharm Res, 2016. 39(1): p. 83-93. 73. Ashino, T., et al., Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth muscle cell migration. Circ Res, 2010. 107(6): p. 787-99. 74. Ashino, T., et al., Copper transporter ATP7A interacts with IQGAP1, a Rac1 binding scaffolding protein: role in PDGF-induced VSMC migration and vascular remodeling. Am J Physiol Cell Physiol, 2018. 315(6): p. C850-C862. 75. Di, R., et al., Silencing PDK1 limits hypoxia-induced pulmonary arterial hypertension in mice via the Akt/p70S6K signaling pathway. Exp Ther Med, 2019. 18(1): p. 699-704. 76. Siavashi, V., et al., Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival. J Cell Biochem, 2017. 118(10): p. 3299-3307. 77. Haider, K.H., S. Aziz, and M.A. Al-Reshidi, Endothelial progenitor cells for cellular angiogenesis and repair: lessons learned from experimental animal models. Regen Med, 2017. 12(8): p. 969-982. 78. Otto, S., et al., Endothelial progenitor cells and plaque burden in stented coronary artery segments: an optical coherence tomography study six months after elective PCI. BMC Cardiovasc Disord, 2017. 17(1): p. 103. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76668 | - |
| dc.description.abstract | 血管再狹窄(restenosis)多好發於經皮冠狀動脈介入治療後，儘管有藥物釋放型支架的發現，支架再狹窄的復發率仍居高不下。而血管中層平滑肌細胞不正常的增生及移行是主要的致病機制，如何減緩這樣的病徵為目前主要研究方向。芫花素(Hydroxygenkwanin, HGK)是從瑞香科植物芫花中萃取出來的黃酮類化合物，在過去抗癌藥物研究已被證實具有抗發炎、抑制細胞增生及移行等效果，但其對於心血管疾病的作用尚未明瞭。本篇研究目的是探討HGK在血管再狹窄病症中，是否具有療效。在細胞實驗以大鼠動脈平滑肌細胞和U937單核球細胞為細胞模式，觀察HGK對於平滑肌細胞增生、移行、黏附及發炎的作用；在動物實驗部分，利用wire injury誘發小鼠股動脈內皮細胞受損為動物損傷模式，觀察HGK是否具有抑制血管內層增生的作用。細胞實驗結果顯示，HGK具有抑制經腫瘤壞死因子刺激細胞發炎及因血小板衍生生長因子誘導細胞增生及移行的作用。此外，得知HGK能透過降低AKT磷酸化而抑制平滑肌細胞的細胞週期調控蛋白表現、肌動蛋白(F-actin)經生長因子誘導的重組反應，及參與降低黏附因子產生的生理機制。後以分子嵌合分析(Molecular docking)發現，HGK與AKT的上游蛋白PDK1之間可能有交互作用關係，故推測HGK可與PDK1作用而抑制AKT磷酸位點的活化，進而抑制平滑肌細胞的生理機制。在動物實驗結果方面，HGK能夠有效抑制血管內皮損傷28天後的內層增生及黏附蛋白的表現，且從伊文斯藍染色及組織免疫化學染色結果，證實HGK能促進血管再內皮化。綜合上述的結果，我們推測HGK可作為支架上塗藥的新選擇。 | zh_TW |
| dc.description.abstract | Blood vessel restenosis is commonly defined as the recurrence of the narrowing of arteries after percutaneous coronary intervention. Despite on-going evolution of drug-eluting stent (DES) technology, the occurrence of in-stent restenosis (ISR) remains relatively unchanged. The abnormal proliferation and migration of smooth muscle cells in the vascular medial layer is the main pathogenesis of the disease. How to slow down such symptoms becomes the core research direction at present. Hydroxygenkwanin (HGK), a nature flavonoid extracted from Daphne genkwa, has been proved to exhibit anti-inflammation, anti-cell proliferation, and cell migration inhibition in previous anti-cancer studies; however, its effects on cardiovascular disease (CVD) still remain unclear. Given to this, this study aims at investigating whether HGK has therapeutic effects on ISR. Rat aortic smooth muscle cells (RASMCs) and U937 cells were used to examine the therapeutic effects of HGK on cell proliferation, migration, adhesion, and anti-inflammation. In addition, supported with the vascular endothelial damage mouse model with C57B/6 mice, we investigated the effect of HGK on neointimal hyperplasia. In vitro, we observed that HGK inhibited the cell inflammation stimulated by tumor necrosis factor (TNF-α), and the proliferation and migration induced by platelet-derived growth factor (PDGF). The results also demonstrated that HGK could hinder the expression of cell cycle regulatory proteins, F-actin rearrangement at the leading edge, and participate in the attenuation of adhesion proteins by reducing AKT phosphorylation. Afterwards, molecular docking analysis suggested that HGK might interact with PDK1, a AKT upstream protein; hence, we supposed that HGK reduce the AKT phosphorylation through PDK1 interaction, which in turn inhibited the physiological mechanism of smooth muscle cells. In vivo, the results showed that neointimal hyperplasia and adhesion proteins expressions were effectively inhibited by HGK intraperitoneal injection on 28 days after injury. In addition, IHC analysis showed that HGK facilitated re-endothelialization in denuded-vessel. Based on the above results, HGK can be used as a new strategy for developing DES. | en |
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| dc.description.tableofcontents | 口試委員會審定書 I 誌謝 II Abstract III 摘要 V 目錄 VI 壹、 緒論 1 一、 前言 1 二、 動脈結構 1 三、 動脈粥狀硬化形成 2 四、 支架再狹窄的成因 2 五、 平滑肌細胞與支架再狹窄化的關係 3 六、 細胞週期與平滑肌增生的關聯 4 七、 細胞骨架與平滑肌移行的關聯 4 八、 平滑肌細胞與單核球細胞的關聯 5 九、 平滑肌增生、移行及發炎之分子機制 5 十、 內皮細胞與血管再內皮化的關係 6 十一、 芫花素(Hydroxygenkwanin)和心血管疾病間的關聯 6 十二、 研究動機和實驗設計 7 貳、 實驗材料 9 一、 儀器設備 9 二、 實驗材料 9 藥品 9 細胞培養 9 結晶紫染色 10 乳酸脫氫酶細胞毒性分析 10 細胞移行 10 西方墨點法 10 流式細胞儀 11 動物實驗 11 免疫細胞化學染色法 11 免疫組織化學染色法 12 三、 溶液配置 12 參、 實驗方法 15 一、 細胞實驗 15 細胞株之培養 15 結晶紫染色分析 15 乳酸脫氫酶細胞毒性分析 15 BrdU incorporation assay 16 細胞傷口癒合分析 16 Phalloidin stain 17 西方墨點法 18 單核球黏附實驗 19 流式細胞儀分析 19 二、 動物實驗 20 動物股動脈去內皮傷害模式 20 動物股動脈冷凍切片 20 Weigert's resorcin fuchsin stain 21 免疫組織化學染色 21 伊文斯藍(Evans blue)染色 22 三、 軟體分析 23 分子嵌合分析 23 數據統計分析 23 肆、 實驗結果 24 一、 HGK對平滑肌細胞的毒性測試 24 二、 HGK具有抑制經PDGF誘導平滑肌細胞增生的功能 24 三、 HGK藉由調控細胞週期抑制平滑肌增生作用 24 四、 HGK具有抑制經PDGF誘導平滑肌細胞移行的功能 25 五、 HGK具有抑制經PDGF誘導板狀偽足形成的功能 25 六、 HGK透過抑制AKT磷酸化降低PDGF誘導平滑肌細胞的增生 26 七、 HGK藉由AKT路徑調控細胞週期蛋白表現 26 八、 HGK藉由抑制AKT磷酸化降低PDGF誘導平滑肌細胞的移行 26 九、 HGK藉由抑制AKT磷酸化降低F-actin於細胞前緣的重組聚集 27 十、 HGK能抑制平滑肌細胞黏附因子生成及單核球的黏附 27 十一、 HGK藉由AKT路徑抑制TNF-α誘導平滑肌細胞生成黏附因子 28 十二、 HGK藉由抑制AKT路徑降低發炎及單核球黏附 28 十三、 HGK與PDK1之間有交互作用關係 29 十四、 HGK具抑制血管受損後異常增厚之功效 29 十五、 HGK能抑制血管中平滑肌細胞的增生 29 十六、 HGK能降低血管中平滑肌細胞經誘導產生的黏附蛋白 30 十七、 HGK具有促進血管再內皮化的效果 30 伍、 討論 31 陸、 附圖 33 圖一、 HGK對平滑肌細胞的毒性測試 33 圖二、 HGK具有抑制經PDGF誘導平滑肌細胞增生的功能 34 圖三、 HGK藉由調控細胞週期抑制平滑肌增生作用 35 圖四、 HGK具有抑制經PDGF誘導平滑肌細胞移行的功能 36 圖五、 HGK具有抑制經PDGF誘導板狀偽足形成的功能 37 圖六、 HGK透過抑制AKT磷酸化降低PDGF誘導平滑肌細胞的增生 38 圖七、 HGK藉由AKT路徑調控細胞週期蛋白表現 39 圖八、 HGK藉由抑制AKT磷酸化降低PDGF誘導平滑肌細胞的移行 41 圖九、 HGK藉由抑制AKT磷酸化降低F-actin於細胞前緣的重組聚集 42 圖十、 HGK能抑制平滑肌細胞黏附因子生成及單核球的黏附 43 圖十一、HGK藉由AKT路徑抑制TNF-α誘導平滑肌細胞生成黏附因子 45 圖十二、 HGK藉由抑制AKT路徑降低發炎及單核球黏附 46 圖十三、 HGK與PDK1之間有交互作用關係 48 圖十四、 HGK具抑制血管受損後異常增厚之功效 49 圖十五、 HGK能抑制血管中平滑肌細胞的增生 50 圖十六、 HGK能降低血管中平滑肌細胞經誘導產生的黏附蛋白 51 圖十七、 HGK具有促進血管再內皮化的效果 52 柒、 參考文獻 54 | |
| dc.language.iso | zh-TW | |
| dc.subject | 血管內層增生 | zh_TW |
| dc.subject | 芫花素 | zh_TW |
| dc.subject | 增生 | zh_TW |
| dc.subject | 移行 | zh_TW |
| dc.subject | 藥物釋放型支架 | zh_TW |
| dc.subject | 支架再狹窄化 | zh_TW |
| dc.subject | drug eluting stent | en |
| dc.subject | neointimal hyperplasia | en |
| dc.subject | in-stent restenosis | en |
| dc.subject | Hydroxygenkwanin | en |
| dc.subject | proliferation | en |
| dc.subject | migration | en |
| dc.title | HGK在血管再狹窄化的治療效果及相關機制 | zh_TW |
| dc.title | The therapeutic effects and the relative mechanisms of Hydroxygenkwanin on restenosis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 龔秀妮(Hsiu-Ni Kung),陳瀅(Ying Chen) | |
| dc.subject.keyword | 芫花素,增生,移行,藥物釋放型支架,支架再狹窄化,血管內層增生, | zh_TW |
| dc.subject.keyword | Hydroxygenkwanin,proliferation,migration,drug eluting stent,in-stent restenosis,neointimal hyperplasia, | en |
| dc.relation.page | 59 | |
| dc.identifier.doi | 10.6342/NTU202004091 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-08-19 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-1908202015492300.pdf 未授權公開取用 | 4.59 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。