(44.192.112.123) 您好!臺灣時間:2021/02/28 05:47
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:陳嘉雄
研究生(外文):Jia-Shiong Chen
論文名稱:銀杏葉萃取物抗動脈粥狀硬化的生成機轉之研究 -從抗氧化能力到增加第一型血色素氧化酵素
論文名稱(外文):Mechanistic Study of Anti-atherogenesis Effect of Ginkgo Biloba Extract - From Antioxidant Property to HO-1 Induction
指導教授:陳肇文陳肇文引用關係
指導教授(外文):Jaw-Wen Chen
學位類別:博士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2011
畢業學年度:100
語文別:英文
論文頁數:106
中文關鍵詞:第一型血色素氧化酶第一型血色素氧化酶第一型血色素氧化酶第一型血色素氧化酶第一型血色素氧化酶第一型血色素氧化酶
外文關鍵詞:Heme oxygenase-1Oxidative stressTNF-alphaHAECAtherogenesisInterlukin 6
相關次數:
  • 被引用被引用:1
  • 點閱點閱:630
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:172
  • 收藏至我的研究室書目清單書目收藏:0
粥狀動脈硬化病理生成的起始過程中,受到化學梯度的趨化素吸引的單核球細胞藉由內皮黏附因子黏附上受損的血管壁,移行進入血管內皮細胞下層,高血糖或發炎因子的刺激促使內皮細胞損傷而造成血管內皮與單核球細胞的黏附增加,內皮黏附因子在這過程中扮演重要角色。抗氧化物具有抑制黏附因子表現,進而降低動脈硬化生成的作用。在本論文中研究銀杏萃取物對於高葡萄糖或細胞激素-腫瘤壞死因子刺激人類動脈內皮細胞黏附因子的影響,探討是否存有抗氧化之外的作用。
臨床研究顯示在糖尿病相關的動脈硬化上高血糖是一個獨立的危險因子。內皮細胞受到高葡萄糖(25 mM)刺激四天時會促使黏附因子表現增加,進而造成單核球細胞與內皮細胞的黏附。在高葡萄糖藉由滲透壓的刺激條件下,內皮細胞氧化壓力上升、細胞激素-IL-6分泌增加、轉錄因子STAT1/3活化,進而增加ICAM-1表現。銀杏萃取物可以減緩高葡萄糖刺激而增加的ICAM-1表現與單核球細胞與內皮細胞的黏附;抗氧化物NAC有類似銀杏萃取物減緩內皮細胞與單核球細胞黏附的效果。所以推測銀杏萃取物可能是透過降低高葡萄糖刺激增加的氧化壓力,進而減緩細胞內黏附因子表現。
銀杏萃取物可以減緩在TNF-α (2 ng/mL)刺激單核球細胞與內皮細胞的黏附,同時給于第一型血紅素氧化脢(HO-1)活性抑制劑:ZnPP IX或是SnPP IX時,銀杏萃取物減緩內皮與單核球細胞沾黏能力就喪失了,這結果推論第一型血紅素氧化脢在銀杏萃取物對抗TNF-α所促使單核球細胞沾黏能力扮演重要的角色。銀杏萃取物透過活化轉錄因子Nrf-2從細胞質移入細胞核,進而結合上第一型血紅素氧化酶基因的ARE (antioxidant response element) 活化位置,促使第一型血紅素氧化酶蛋白質生成增加,訊息傳遞機制推測可能是透過p38/Nrf-2路徑,而氧化壓力可能並無直接參與。所以銀杏萃取物透過選擇性的路徑增加第一型血紅素氧化酶生成而達到抗血管發炎。在動物實驗結果顯示,銀杏萃取物可以減緩股動脈損傷所造成單核球細胞黏附血管壁,同時可以增加損傷後的血管組織與單核球細胞第一型血紅素氧化酶生成。
根據實驗的結果推論,銀杏萃取物在保護內皮細胞在長時間處理高葡萄糖時,減緩單核球細胞沾黏的效果與減少氧化壓力有關。而在處理TNF-α時,銀杏萃取物對抗血管發炎的效果透過增加第一型血紅素氧化酶。因此提出一個新的機制在銀杏萃取物對抗粥狀動脈硬化生成與其他發炎反應。

An important initial event in the pathogenesis of atherosclerosis is adhesion of monocytes to arterial endothelial cells, followed by their transmigration into the sub-endothelial space along a chemotactic gradient. Endothelial adhesion molecules take part in this event and play important roles in atherogenesis. Hyperglycemia or proinflammatory cytokines have been proposed to trigger endothelial oxidative stress, facilitate monocyte adhesion to endothelial cells. Suppression of endothelial adhesion molecules by antioxidant agents have attenuated the processes leading to atherogenesis. In this study, ginkgo biloba extract (GBE) was used to suppress the high glucose- or TNF-α-induced expression of adhesion molecules in HAECs. The effect of GBE-induced HO-1 (heme oxygenase-1) on anti-atherogenesis was also investigated.
Clinical evidence suggests that hyperglycemia is an independent risk factor of diabetes-associated atherosclerosis. Exposure to high glucose (25mM) for 4 days induced expression of ICAM-1, enhancing monocyte adhesion to HAECs. High glucose treatment for 3 days, followed by treatment with GBE for 1 day, reduced high glucose-induced ROS generation, IL-6 secretion, IL-6-medilated activation of signal transducer and activator of transcription 1/3 (STAT1/3), and ICAM-1 accumulation in HAECs. NAC, an antioxidant agent, had a similar effect on suppressing high glucose-activated IL-6 secretion, ICAM-1 accumulation, and endothelial adhesiveness. These findings support the notion that GBE may use an antioxidant mechanism to inhibit intracellular redox-sensitive transcription pathways.
Pretreatment with GBE for 12 hours reduced TNF-α-stimulated endothelial adhesion, which could be attenuated by HO-1 inhibitors ZnPP IX or SnPP IX. These results suggest HO-1 plays a crucial role in GBE induced suppression of TNF-α-mediated monocyte adhesion. Furthermore, GBE induced expression of HO-1 by activating the translocation of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and increasing its binding to the antioxidant response element (ARE) of the HO-1 promoter gene. In vivo study also showed that GBE treatment could reduce leukocyte adherence to injured arteries, and enhance HO-1 expression in circulating monocytes as well as in arteries after wire injury. These findings suggest that GBE could inhibit cytokine-induced endothelial adhesion by inducing HO-1 expression via activation of p38 and Nrf-2 pathways, a mechanism in which oxidative stress is not directly involved. GBE might exert its anti-atherogenesis and vascular protective effects by inducing vascular HO-1 expression.
These results suggest that the anti-atherogenic effect of GBE against HAECs under chronic exposure to high glucose is through antioxidant-dependent mechanism. The GBE augmented anti-atherogenic effect also involves inhibition of ROS-sensitive transcriptional pathways in high glucose-stimulated HAECs. Furthermore, in TNF-α-stimulated HAECs, GBE promotes anti-atherogenesis by directly inducing HO-1 transcriptional pathways.

國立陽明大學學位論文電子檔著作權授權書、國家圖書館碩博士論文電子檔
案上網授權書
國立陽明大學 學位論文電子檔審定證明書
國立陽明大學 博士論文學位審定同意書
Acknowledgement
Contents 2
中文摘要 3
English abstract 5
List of abbreviations 8
Introduction 10
Hypothesis and aim of study 21
Materials and methods 26
Results 38
Discussions 57
Conclusion 70
References 72
Figures 83
Publications 106

1.Hansson GK. Inflammation, atherosclerosis, and coronary
artery disease. N Engl J Med. 2005;352:1685-1695.
2.Packard RR, Libby P. Inflammation in atherosclerosis: from
vascular biology to biomarker discovery and risk
prediction. Clin Chem. 2008;54:24-38.
3.Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D,
Cybulsky MI. Low-grade chronic inflammation in regions of
the normal mouse arterial intima predisposed to
atherosclerosis. J Exp Med. 2006;203:2073-2083.
4.Hansson GK, Robertson AK, Soderberg-Naucler C.
Inflammation and atherosclerosis. Annu Rev Pathol.
2006;1:297-329.
5.Altman R. Risk factors in coronary atherosclerosis athero-
inflammation: the meeting point. Thromb J. 2003;1:4.
6.Tedgui A, Mallat Z. Cytokines in atherosclerosis:
pathogenic and regulatory pathways. Physiol Rev.
2006;86:515-581.
7.Cybulsky MI, Gimbrone MA, Jr. Endothelial expression of a
mononuclear leukocyte adhesion molecule during
atherogenesis. Science.1991;251:788-791.
8.Nakashima Y, Raines EW, Plump AS, Breslow JL, Ross R.
Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone
sites on the endothelium in the ApoE-deficient mouse.
Arterioscler Thromb Vasc Biol. 1998;18:842-851.
9.Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M,
Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS. A
major role for VCAM-1, but not ICAM-1, in early
atherosclerosis. J Clin Invest. 2001;107:1255-1262.
10.Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O,
Innerarity TL, Boren J. Subendothelial retention of
atherogenic lipoproteins in early atherosclerosis. Nature.
2002;417:750-754.
11.Leitinger N. Oxidized phospholipids as modulators of
inflammation in atherosclerosis. Curr Opin Lipidol.
2003;14:421-430.
12.Newby AC. An overview of the vascular response to injury:
a tribute to the late Russell Ross. Toxicol Lett.
2000;112-113:519-529.
13.Kirkby NS, Low L, Seckl JR, Walker BR, Webb DJ, Hadoke
PW. Quantitative 3-dimensional imaging of murine
neointimal and atherosclerotic lesions by optical
projection tomography. PLoS One;6:e16906.
14.Orford JL, Selwyn AP, Ganz P, Popma JJ, Rogers C. The
comparative pathobiology of atherosclerosis and
restenosis. Am J Cardiol. 2000;86:6H-11H.
15.Davis C, Fischer J, Ley K, Sarembock IJ. The role of
inflammation in vascular injury and repair. J Thromb
Haemost. 2003;1:1699-1709.
16.Kyriakis JM. Activation of the AP-1 transcription factor
by inflammatory cytokines of the TNF family. Gene Expr.
1999;7:217-231.
17.DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M. A
cytokine-responsive IkappaB kinase that activates the
transcription factor NF-kappaB. Nature. 1997;388:548-554.
18.Ohta H, Wada H, Niwa T, Kirii H, Iwamoto N, Fujii H,
Saito K, Sekikawa K, Seishima M. Disruption of tumor
necrosis factor-alpha gene diminishes the development of
atherosclerosis in ApoE-deficient mice. Atherosclerosis.
2005;180:11-17.
19.Beg AA FT, Nantermet PV, Baldwin AS. . Tumor necrosis
factor and interleukin-1 lead to phosphorylation and loss
of I kappa B alpha: a mechanism for NF-kappa B
activation. . Mol Cell Biol. 1993;13:3301–3310.
20.Westwick JK, Weitzel C, Minden A, Karin M, Brenner DA.
Tumor necrosis factor alpha stimulates AP-1 activity
through prolonged activation of the c-Jun kinase. J Biol
Chem. 1994;269:26396-26401.
21.Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky
MI. The NF-kappa B signal transduction pathway in aortic
endothelial cells is primed for activation in regions
predisposed to atherosclerotic lesion formation. Proc
Natl Acad Sci U S A. 2000;97:9052-9057.
22.Chen JW, Chen YH, Lin FY, Chen YL, Lin SJ. Ginkgo biloba
extract inhibits tumor necrosis factor-alpha-induced
reactive oxygen species generation, transcription factor
activation, and cell adhesion molecule expression in
human aortic endothelial cells. Arterioscler Thromb Vasc
Biol. 2003;23:1559-1566.
23.Chen K, Vita JA, Berk BC, Keaney JF, Jr. c-Jun N-terminal
kinase activation by hydrogen peroxide in endothelial
cells involves SRC-dependent epidermal growth factor
receptor transactivation. J Biol Chem. 2001;276:16045-
16050.
24.Lakshminarayanan V, Drab-Weiss EA, Roebuck KA. H2O2 and
tumor necrosis factor-alpha induce differential binding
of the redox-responsive transcription factors AP-1 and
NF-kappaB to the interleukin-8 promoter in endothelial
and epithelial cells. J Biol Chem. 1998;273:32670-32678.
25.Csiszar A, Labinskyy N, Smith K, Rivera A, Orosz Z,
Ungvari Z. Vasculoprotective effects of anti-tumor
necrosis factor-alpha treatment in aging. Am J Pathol.
2007;170:388-398.
26.Li JM, Mullen AM, Yun S, Wientjes F, Brouns GY, Thrasher
AJ, Shah AM. Essential role of the NADPH oxidase subunit
p47(phox) in endothelial cell superoxide production in
response to phorbol ester and tumor necrosis factor-
alpha. Circ Res. 2002;90:143-150.
27.Li JM, Fan LM, Christie MR, Shah AM. Acute tumor necrosis
factor alpha signaling via NADPH oxidase in microvascular
endothelial cells: role of p47phox phosphorylation and
binding to TRAF4. Mol Cell Biol. 2005;25:2320-2330.
28.Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M.
Mortality from coronary heart disease in subjects with
type 2 diabetes and in nondiabetic subjects with and
without prior myocardial infarction. N Engl J Med.
1998;339:229-234.
29.Nakagami H, Kaneda Y, Ogihara T, Morishita R. Endothelial
dysfunction in hyperglycemia as a trigger of
atherosclerosis. Curr Diabetes Rev. 2005;1:59-63.
30.Brown A, Reynolds LR, Bruemmer D. Intensive glycemic
control and cardiovascular disease: an update. Nat Rev
Cardiol;7:369-375.
31.Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM,
Orchard TJ, Raskin P, Zinman B. Intensive diabetes
treatment and cardiovascular disease in patients with
type 1 diabetes. N Engl J Med. 2005;353:2643-2653.
32.Bornfeldt KE, Tabas I. Insulin resistance, hyperglycemia,
and atherosclerosis. Cell Metab;14:575-585.
33.Cipolletta C, Ryan KE, Hanna EV, Trimble ER. Activation
of peripheral blood CD14+ monocytes occurs in diabetes.
Diabetes. 2005;54:2779-2786.
34.Kanter JE, Johansson F, LeBoeuf RC, Bornfeldt KE. Do
glucose and lipids exert independent effects on
atherosclerotic lesion initiation or progression to
advanced plaques? Circ Res. 2007;100:769-781.
35.Nakagami H, Liao JK. Statins and myocardial hypertrophy.
Coron Artery Dis. 2004;15:247-250.
36.Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ,
Walker S, Shah AM. NADPH oxidases in cardiovascular
health and disease. Antioxid Redox Signal. 2006;8:691-
728.
37.Ceriello A, Falleti E, Motz E, Taboga C, Tonutti L, Ezsol
Z, Gonano F, Bartoli E. Hyperglycemia-induced circulating
ICAM-1 increase in diabetes mellitus: the possible role
of oxidative stress. Horm Metab Res. 1998;30:146-149.
38.Marfella R, Quagliaro L, Nappo F, Ceriello A, Giugliano
D. Acute hyperglycemia induces an oxidative stress in
healthy subjects. J Clin Invest. 2001;108:635-636.
39.Kado S, Wakatsuki T, Yamamoto M, Nagata N. Expression of
intercellular adhesion molecule-1 induced by high glucose
concentrations in human aortic endothelial cells. Life
Sci. 2001;68:727-737.
40.Srinivasan S, Hatley ME, Reilly KB, Danziger EC, Hedrick
CC. Modulation of PPARalpha expression and inflammatory
interleukin-6 production by chronic glucose increases
monocyte/endothelial adhesion. Arterioscler Thromb Vasc
Biol. 2004;24:851-857.
41.Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3
in inflammation and cancer. Eur J Cancer. 2005;41:2502-
2512.
42.Masha A, Brocato L, Dinatale S, Mascia C, Biasi F,
Martina V. N-acetylcysteine is able to reduce the
oxidation status and the endothelial activation after a
high-glucose content meal in patients with Type 2
diabetes mellitus. J Endocrinol Invest. 2009;32:352-356.
43.Morigi M, Angioletti S, Imberti B, Donadelli R,
Micheletti G, Figliuzzi M, Remuzzi A, Zoja C, Remuzzi G.
Leukocyte-endothelial interaction is augmented by high
glucose concentrations and hyperglycemia in a NF-kB-
dependent fashion. J Clin Invest. 1998;101:1905-1915.
44.Foncea R, Carvajal C, Almarza C, Leighton F. Endothelial
cell oxidative stress and signal transduction. Biol Res.
2000;33:89-96.
45.Shiao MS, Chiu JJ, Chang BW, Wang J, Jen WP, Wu YJ, Chen
YL. In search of antioxidants and anti-atherosclerotic
agents from herbal medicines. Biofactors. 2008;34:147-
157.
46.Lin SJ, Shyue SK, Liu PL, Chen YH, Ku HH, Chen JW, Tam
KB, Chen YL. Adenovirus-mediated overexpression of
catalase attenuates oxLDL-induced apoptosis in human
aortic endothelial cells via AP-1 and C-Jun N-terminal
kinase/extracellular signal-regulated kinase mitogen-
activated protein kinase pathways. J Mol Cell Cardiol.
2004;36:129-139.
47.Lin SJ, Shyue SK, Shih MC, Chu TH, Chen YH, Ku HH, Chen
JW, Tam KB, Chen YL. Superoxide dismutase and catalase
inhibit oxidized low-density lipoprotein-induced human
aortic smooth muscle cell proliferation: role of cell-
cycle regulation, mitogen-activated protein kinases, and
transcription factors. Atherosclerosis. 2007;190:124-134.
48.Csiszar A, Smith K, Labinskyy N, Orosz Z, Rivera A,
Ungvari Z. Resveratrol attenuates TNF-alpha-induced
activation of coronary arterial endothelial cells: role
of NF-kappaB inhibition. Am J Physiol Heart Circ Physiol.
2006;291:H1694-1699.
49.Ludwig A, Lorenz M, Grimbo N, Steinle F, Meiners S,
Bartsch C, Stangl K, Baumann G, Stangl V. The tea
flavonoid epigallocatechin-3-gallate reduces cytokine-
induced VCAM-1 expression and monocyte adhesion to
endothelial cells. Biochem Biophys Res Commun.
2004;316:659-665.
50.Chen YH, Lin SJ, Chen JW, Ku HH, Chen YL. Magnolol
attenuates VCAM-1 expression in vitro in TNF-alpha-
treated human aortic endothelial cells and in vivo in the
aorta of cholesterol-fed rabbits. Br J Pharmacol.
2002;135:37-47.
51.Yang H, Shi M, Richardson A, Vijg J, Guo Z. Attenuation
of leukocyte-endothelium interaction by antioxidant
enzymes. Free Radic Biol Med. 2003;35:266-276.
52.Lehr HA, Becker M, Marklund SL, Hubner C, Arfors KE,
Kohlschutter A, Messmer K. Superoxide-dependent
stimulation of leukocyte adhesion by oxidatively modified
LDL in vivo. Arterioscler Thromb. 1992;12:824-829.
53.Lin SJ, Shyue SK, Hung YY, Chen YH, Ku HH, Chen JW, Tam
KB, Chen YL. Superoxide dismutase inhibits the expression
of vascular cell adhesion molecule-1 and intracellular
cell adhesion molecule-1 induced by tumor necrosis
factor-alpha in human endothelial cells through the
JNK/p38 pathways. Arterioscler Thromb Vasc Biol.
2005;25:334-340.
54.Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T,
Ohta K, Kasahara Y, Koizumi S. Oxidative stress causes
enhanced endothelial cell injury in human heme oxygenase-
1 deficiency. J Clin Invest. 1999;103:129-135.
55.Ray R, Shah AM. NADPH oxidase and endothelial cell
function. Clin Sci (Lond). 2005;109:217-226.
56.Torzewski M, Ochsenhirt V, Kleschyov AL, Oelze M, Daiber
A, Li H, Rossmann H, Tsimikas S, Reifenberg K, Cheng F,
Lehr HA, Blankenberg S, Forstermann U, Munzel T, Lackner
KJ. Deficiency of glutathione peroxidase-1 accelerates
the progression of atherosclerosis in apolipoprotein E-
deficient mice. Arterioscler Thromb Vasc Biol.
2007;27:850-857.
57.Morita T. Heme oxygenase and atherosclerosis.
Arterioscler Thromb Vasc Biol. 2005;25:1786-1795.
58.Kim YM, Pae HO, Park JE, Lee YC, Woo JM, Kim NH, Choi YK,
Lee BS, Kim SR, Chung HT. Heme oxygenase in the
regulation of vascular biology: from molecular mechanisms
to therapeutic opportunities. Antioxid Redox
Signal.2010;14:137-167.
59.Turkseven S, Kruger A, Mingone CJ, Kaminski P, Inaba M,
Rodella LF, Ikehara S, Wolin MS, Abraham NG. Antioxidant
mechanism of heme oxygenase-1 involves an increase in
superoxide dismutase and catalase in experimental
diabetes. Am J Physiol Heart Circ Physiol. 2005;289:H701-
707.
60.Duckers HJ, Boehm M, True AL, Yet SF, San H, Park JL,
Clinton Webb R, Lee ME, Nabel GJ, Nabel EG. Heme
oxygenase-1 protects against vascular constriction and
proliferation. Nat Med. 2001;7:693-698.
61.Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk
M, Davis RJ, Flavell RA, Choi AM. Carbon monoxide has
anti-inflammatory effects involving the mitogen-activated
protein kinase pathway. Nat Med. 2000;6:422-428.
62.Llesuy SF, Tomaro ML. Heme oxygenase and oxidative
stress. Evidence of involvement of bilirubin as
physiological protector against oxidative damage. Biochim
Biophys Acta. 1994;1223:9-14.
63.Miguel P. Soares MPS, Isabel Pombo Gregoire, Tatiana
Vassilevskaia,, Pascal O. Berberat JY, Tung-Yu Tsui, and
Fritz H. Bach. Heme oxygenase-1 modulates the expression
of adhesion molecules associated with endothelial cell
activation. The Journal of Immunology, . 2004;172:3553–
3563.
64.Ishikawa K, Sugawara D, Wang X, Suzuki K, Itabe H,
Maruyama Y, Lusis AJ. Heme oxygenase-1 inhibits
atherosclerotic lesion formation in ldl-receptor knockout
mice. Circ Res. 2001;88:506-512.
65.Yet SF, Layne MD, Liu X, Chen YH, Ith B, Sibinga NE,
Perrella MA. Absence of heme oxygenase-1 exacerbates
atherosclerotic lesion formation and vascular remodeling.
Faseb J. 2003;17:1759-1761.
66.Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau
LY. Adenovirus-mediated heme oxygenase-1 gene transfer
inhibits the development of atherosclerosis in
apolipoprotein E-deficient mice. Circulation.
2001;104:1519-1525.
67.Wu L, Wang R. Carbon monoxide: endogenous production,
physiological functions, and pharmacological
applications. Pharmacol Rev. 2005;57:585-630.
68.Foresti R, Clark JE, Green CJ, Motterlini R. Thiol
compounds interact with nitric oxide in regulating heme
oxygenase-1 induction in endothelial cells. Involvement
of superoxide and peroxynitrite anions. J Biol Chem.
1997;272:18411-18417.
69.Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K,
Engel JD, Yamamoto M. Keap1 represses nuclear activation
of antioxidant responsive elements by Nrf2 through
binding to the amino-terminal Neh2 domain. Genes Dev.
1999;13:76-86.
70.Chen XL, Dodd G, Thomas S, Zhang X, Wasserman MA, Rovin
BH, Kunsch C. Activation of Nrf2/ARE pathway protects
endothelial cells from oxidant injury and inhibits
inflammatory gene expression. Am J Physiol Heart Circ
Physiol. 2006;290:H1862-1870.
71.Nakaso K, Nakamura C, Sato H, Imamura K, Takeshima T,
Nakashima K. Novel cytoprotective mechanism of anti-
parkinsonian drug deprenyl: PI3K and Nrf2-derived
induction of antioxidative proteins. Biochem Biophys Res
Commun. 2006;339:915-922.
72.Andreadi CK, Howells LM, Atherfold PA, Manson MM.
Involvement of Nrf2, p38, B-Raf, and nuclear factor-
kappaB, but not phosphatidylinositol 3-kinase, in
induction of hemeoxygenase-1 by dietary polyphenols. Mol
Pharmacol. 2006;69:1033-1040.
73.McNally SJ, Harrison EM, Ross JA, Garden OJ, Wigmore SJ.
Curcumin induces heme oxygenase 1 through generation of
reactive oxygen species, p38 activation and phosphatase
inhibition. Int J Mol Med. 2007;19:165-172.
74.Lee TS, Chang CC, Zhu Y, Shyy JY. Simvastatin induces
heme oxygenase-1: a novel mechanism of vessel protection.
Circulation. 2004;110:1296-1302.
75.Wu BJ, Kathir K, Witting PK, Beck K, Choy K, Li C, Croft
KD, Mori TA, Tanous D, Adams MR, Lau AK, Stocker R.
Antioxidants protect from atherosclerosis by a heme
oxygenase-1 pathway that is independent of free radical
scavenging. J Exp Med. 2006;203:1117-1127.
76.Kleijnen J, Knipschild P. Ginkgo biloba. Lancet.
1992;340:1136-1139.
77.Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM,
Schatzberg AF. A placebo-controlled, double-blind,
randomized trial of an extract of Ginkgo biloba for
dementia. North American EGb Study Group. Jama.
1997;278:1327-1332.
78.Varga E, Bodi A, Ferdinandy P, Droy-Lefaix MT, Blasig IE,
Tosaki A. The protective effect of EGb 761 in isolated
ischemic/reperfused rat hearts: a link between cardiac
function and nitric oxide production. J Cardiovasc
Pharmacol. 1999;34:711-717.
79.Sastre J, Millan A, Garcia de la Asuncion J, Pla R, Juan
G, Pallardo, O'Connor E, Martin JA, Droy-Lefaix MT, Vina
J. A Ginkgo biloba extract (EGb 761) prevents
mitochondrial aging by protecting against oxidative
stress. Free Radic Biol Med. 1998;24:298-304.
80.Lin FY, Chen YH, Chen YL, Wu TC, Li CY, Chen JW, Lin SJ.
Ginkgo biloba extract inhibits endotoxin-induced human
aortic smooth muscle cell proliferation via suppression
of toll-like receptor 4 expression and NADPH oxidase
activation. J Agric Food Chem. 2007;55:1977-1984.
81.Lin SJ, Yang TH, Chen YH, Chen JW, Kwok CF, Shiao MS,
Chen YL. Effects of Ginkgo biloba extract on the
proliferation of vascular smooth muscle cells in vitro
and on intimal thickening and interleukin-1beta
expression after balloon injury in cholesterol-fed
rabbits in vivo. J Cell Biochem. 2002;85:572-582.
82.Gertz HJ, Kiefer M. Review about Ginkgo biloba special
extract EGb 761 (Ginkgo). Curr Pharm Des. 2004;10:261-
264.
83.Hsu CL, Wu YL, Tang GJ, Lee TS, Kou YR. Ginkgo biloba
extract confers protection from cigarette smoke extract-
induced apoptosis in human lung endothelial cells: Role
of heme oxygenase-1. Pulm Pharmacol Ther. 2009;22:286-
296.
84.Saleem S, Zhuang H, Biswal S, Christen Y, Dore S. Ginkgo
biloba extract neuroprotective action is dependent on
heme oxygenase 1 in ischemic reperfusion brain injury.
Stroke. 2008;39:3389-3396.
85.Tsai JY, Su KH, Shyue SK, Kou YR, Yu YB, Hsiao SH, Chiang
AN, Wu YL, Ching LC, Lee TS. EGb761 ameliorates the
formation of foam cells by regulating the expression of
SR-A and ABCA1: role of haem oxygenase-1. Cardiovasc Res.
2010;88: 415-423.
86.Abraham NG, Drummond G. CD163-Mediated hemoglobin-heme
uptake activates macrophage HO-1, providing an
antiinflammatory function. Circ Res. 2006;99:911-914.
87.Farombi EO, Surh YJ. Heme oxygenase-1 as a potential
therapeutic target for hepatoprotection. J Biochem Mol
Biol. 2006;39:479-491.
88.Chang YJ, Holtzman MJ, Chen CC. Interferon-gamma-induced
epithelial ICAM-1 expression and monocyte adhesion.
Involvement of protein kinase C-dependent c-Src tyrosine
kinase activation pathway. J Biol Chem. 2002;277:7118-
7126.
89.Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F,
Eaton JW, Vercellotti GM. Ferritin: a cytoprotective
antioxidant strategem of endothelium. J Biol Chem.
1992;267:18148-18153.
90.Wang CH, Verma S, Hsieh IC, Hung A, Cheng TT, Wang SY,
Liu YC, Stanford WL, Weisel RD, Li RK, Cherng WJ. Stem
cell factor attenuates vascular smooth muscle apoptosis
and increases intimal hyperplasia after vascular injury.
Arterioscler Thromb Vasc Biol. 2007;27:540-547.
91.Takami S, Yamashita S, Kihara S, Kameda-Takemura K,
Matsuzawa Y. High concentration of glucose induces the
expression of intercellular adhesion molecule-1 in human
umbilical vein endothelial cells. Atherosclerosis.
1998;138:35-41.
92.Kaplanski G, Marin V, Montero-Julian F, Mantovani A,
Farnarier C. IL-6: a regulator of the transition from
neutrophil to monocyte recruitment during inflammation.
Trends Immunol. 2003;24:25-29.
93.Srinivasan S, Hatley ME, Bolick DT, Palmer LA, Edelstein
D, Brownlee M, Hedrick CC. Hyperglycaemia-induced
superoxide production decreases eNOS expression via AP-1
activation in aortic endothelial cells. Diabetologia.
2004;47:1727-1734.
94.Nguyen T, Sherratt PJ, Pickett CB. Regulatory mechanisms
controlling gene expression mediated by the antioxidant
response element. Annu Rev Pharmacol Toxicol.
2003;43:233-260.
95.Kevil CG, Patel RP, Bullard DC. Essential role of ICAM-1
in mediating monocyte adhesion to aortic endothelial
cells. Am J Physiol Cell Physiol. 2001;281:C1442-1447.
96.Wung BS, Hsu MC, Wu CC, Hsieh CW. Resveratrol suppresses
IL-6-induced ICAM-1 gene expression in endothelial cells:
effects on the inhibition of STAT3 phosphorylation. Life
Sci. 2005;78:389-397.
97.Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D,
Esposito K, Szabo C, Ceriello A. Intermittent high
glucose enhances ICAM-1, VCAM-1, E-selectin and
interleukin-6 expression in human umbilical endothelial
cells in culture: the role of poly(ADP-ribose)
polymerase. J Thromb Haemost. 2004;2:1453-1459.
98.Park CW, Kim JH, Lee JH, Kim YS, Ahn HJ, Shin YS, Kim SY,
Choi EJ, Chang YS, Bang BK. High glucose-induced
intercellular adhesion molecule-1 (ICAM-1) expression
through an osmotic effect in rat mesangial cells is PKC-
NF-kappa B-dependent. Diabetologia. 2000;43:1544-1553.
99.Lenardo MJ, Baltimore D. NF-kappa B: a pleiotropic
mediator of inducible and tissue-specific gene control.
Cell. 1989;58:227-229.
100.Kevil CG, Bullard DC. Roles of leukocyte/endothelial
cell adhesion molecules in the pathogenesis of
vasculitis. Am J Med. 1999;106:677-687.
101.Petruzzelli L, Takami M, Humes HD. Structure and
function of cell adhesion molecules. Am J Med.
1999;106:467-476.
102.Yoshikawa T, Yoshida N. Vitamin E and leukocyte-
endothelial cell interactions. Antioxid Redox Signal.
2000;2:821-825.
103.Chen YH, Lin SJ, Chen YL, Liu PL, Chen JW. Anti-
inflammatory effects of different drugs/agents with
antioxidant property on endothelial expression of
adhesion molecules. Cardiovasc Hematol Disord Drug
Targets. 2006;6:279-304.
104.Chen SC, Chang YL, Wang DL, Cheng JJ. Herbal remedy
magnolol suppresses IL-6-induced STAT3 activation and
gene expression in endothelial cells. Br J Pharmacol.
2006;148:226-232.
105.Dimitrova Y, Dunoyer-Geindre S, Reber G, Mach F,
Kruithof EK, de Moerloose P. Effects of statins on
adhesion molecule expression in endothelial cells. J
Thromb Haemost. 2003;1:2290-2299.
106.Chen YH, Lin SJ, Ku HH, Shiao MS, Lin FY, Chen JW, Chen
YL. Salvianolic acid B attenuates VCAM-1 and ICAM-1
expression in TNF-alpha-treated human aortic endothelial
cells. J Cell Biochem. 2001;82:512-521.
107.Romano M, Sironi M, Toniatti C, Polentarutti N,
Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh
V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani
A. Role of IL-6 and its soluble receptor in induction of
chemokines and leukocyte recruitment. Immunity.
1997;6:315-325.
108.Zhang L, Zalewski A, Liu Y, Mazurek T, Cowan S, Martin
JL, Hofmann SM, Vlassara H, Shi Y. Diabetes-induced
oxidative stress and low-grade inflammation in porcine
coronary arteries. Circulation. 2003;108:472-478.
109.Rodriguez M, Ringstad L, Schafer P, Just S, Hofer HW,
Malmsten M, Siegel G. Reduction of atherosclerotic
nanoplaque formation and size by Ginkgo biloba (EGb 761)
in cardiovascular high-risk patients. Atherosclerosis.
2007;192:438-444.
110.Ji L, Yin XX, Wu ZM, Wang JY, Lu Q, Gao YY. Ginkgo
biloba extract prevents glucose-induced accumulation of
ECM in rat mesangial cells. Phytother Res. 2009;23:477-
485.
111.Wu ZM, Yin XX, Ji L, Gao YY, Pan YM, Lu Q, Wang JY.
Ginkgo biloba extract prevents against apoptosis induced
by high glucose in human lens epithelial cells. Acta
Pharmacol Sin. 2008;29:1042-1050.
112.Booth G, Stalker TJ, Lefer AM, Scalia R. Mechanisms of
amelioration of glucose-induced endothelial dysfunction
following inhibition of protein kinase C in vivo.
Diabetes. 2002;51:1556-1564.
113.Hishikawa K, Nakaki T, Fujita T. Oral flavonoid
supplementation attenuates atherosclerosis development in
apolipoprotein E-deficient mice. Arterioscler Thromb Vasc
Biol. 2005;25:442-446.
114.Kaga S, Zhan L, Matsumoto M, Maulik N. Resveratrol
enhances neovascularization in the infarcted rat
myocardium through the induction of thioredoxin-1, heme
oxygenase-1 and vascular endothelial growth factor. J Mol
Cell Cardiol. 2005;39:813-822.
115.Jeong GS, Oh GS, Pae HO, Jeong SO, Kim YC, Shin MK, Seo
BY, Han SY, Lee HS, Jeong JG, Koh JS, Chung HT.
Comparative effects of curcuminoids on endothelial heme
oxygenase-1 expression: ortho-methoxy groups are
essential to enhance heme oxygenase activity and
protection. Exp Mol Med. 2006;38:393-400.
116.Wung BS, Hsu MC, Wu CC, Hsieh CW. Piceatannol
upregulates endothelial heme oxygenase-1 expression via
novel protein kinase C and tyrosine kinase pathways.
Pharmacol Res. 2006;53:113-122.
117.Lee SE, Jeong SI, Yang H, Park CS, Jin YH, Park YS.
Fisetin induces Nrf2-mediated HO-1 expression through
PKC-delta and p38 in human umbilical vein endothelial
cells. J Cell Biochem. 2011;112;2352–2360.
118.Lim HJ, Lee KS, Lee S, Park JH, Choi HE, Go SH, Kwak HJ,
Park HY. 15d-PGJ(2) stimulates HO-1 expression through
p38 MAP kinase and Nrf-2 pathway in rat vascular smooth
muscle cells. Toxicol Appl Pharmacol. 2007;223:20-27.
119.Yao P, Nussler A, Liu L, Hao L, Song F, Schirmeier A,
Nussler N. Quercetin protects human hepatocytes from
ethanol-derived oxidative stress by inducing heme
oxygenase-1 via the MAPK/Nrf2 pathways. J Hepatol.
2007;47:253-261.
120.Sata M, Maejima Y, Adachi F, Fukino K, Saiura A, Sugiura
S, Aoyagi T, Imai Y, Kurihara H, Kimura K, Omata M,
Makuuchi M, Hirata Y, Nagai R. A mouse model of vascular
injury that induces rapid onset of medial cell apoptosis
followed by reproducible neointimal hyperplasia. J Mol
Cell Cardiol. 2000;32:2097-2104.
121.Zimmerman MA, Selzman CH, Reznikov LL, Miller SA,
Raeburn CD, Emmick J, Meng X, Harken AH. Lack of TNF-
alpha attenuates intimal hyperplasia after mouse carotid
artery injury. Am J Physiol Regul Integr Comp Physiol.
2002;283:R505-512.
122.Wadsworth TL, Koop DR. Effects of Ginkgo biloba extract
(EGb 761) and quercetin on lipopolysaccharide-induced
release of nitric oxide. Chem Biol Interact. 2001;137:43-
58.
123.Birks J, Grimley Evans J. Ginkgo biloba for cognitive
impairment and dementia. Cochrane Database Syst Rev.
2007:CD003120.
124.Soares MP, Seldon MP, Gregoire IP, Vassilevskaia T,
Berberat PO, Yu J, Tsui TY, Bach FH. Heme oxygenase-1
modulates the expression of adhesion molecules associated
with endothelial cell activation. J Immunol.
2004;172:3553-3563.

連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔