(54.236.58.220) 您好!臺灣時間:2021/03/09 16:54
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:陳雅雯
研究生(外文):Ya-Wen Chen
論文名稱:碳六十化合物C60(OH)9±2保護RAW264.7細胞及失血-再灌流的游離肺所遭受之氧化性傷害
論文名稱(外文):Fullerene derivative protects against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs.
指導教授:賴義隆賴義隆引用關係
指導教授(外文):Yih-Loong Lai
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
中文關鍵詞:碳六十氧化性傷害失血-再灌流
外文關鍵詞:fullereneoxidative stressischemia-reperfusionlung
相關次數:
  • 被引用被引用:1
  • 點閱點閱:131
  • 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:19
  • 收藏至我的研究室書目清單書目收藏:0
碳六十化合物目前已被證實為一有效的氧自由基 (reactive oxygen species, ROS) 的清除劑,本實驗設計的主要研究目的為測試含有氫氧官能基 (-OH groups) 的碳六十化合物polyhydroxylated fullerene derivate C60(OH)9±2 對於RAW 264.7 細胞培養株及失血之後予以再灌流 (ischemia-reperfusion, IR) 的游離肺 (isolated lung) 中所遭受的氧化性傷害 (oxidative stress) 是否具有保護性的作用。
我們在實驗中使用sodium nitroprusside (SNP) 及H2O2分別提高在RAW 264.7細胞培養液中的一氧化氮 (nitric oxide, NO) 及氧化物 (oxidants)。此外,在游離肺進行失血之後予以再灌流的步驟中,我們的觀察目標共分為3個時期:基線時期 (baseline) ,缺血時期 (ischemia),以及再灌流時期 (reperfusion)。
實驗結果發現,在RAW 264.7 細胞,SNP (1 mM) 或H2O2 (400 mM) 導致細胞存活率下降至90﹪,而隨著 C60(OH)9±2 加入的濃度越高,細胞存活率有明顯提升的現象,與濃度是正相關的關係。另一方面,經由SNP或H2O2 所引發的ROS增加,也能經由C60(OH)9±2 的加入而減少。此外,經由SNP或H2O2 所導致的粒腺體膜電位 (mitochondria membrane potential) 下降的現象也能被 C60(OH)9±2 逆轉。然而,高濃度的 C60(OH)9±2 (1, 1.5 mM) 卻會導致細胞死亡。 在游離肺中,我們也發現在IR進行過程中由SNP所引發的肺動脈壓 (pulmonary artery pressure, Pa) 及肺微血管過濾壓 (pulmonary capillary filtration pressure) 之增高,能被 C60(OH)9±2 減低。
經由以上實驗結果,證明了低濃度的碳六十化合物C60(OH)9±2 可以保護RAW 264.7 細胞培養株及失血-再灌流的游離肺所遭受的氧化性傷害。

Fullerene derivatives have often been used as effective scavengers for reactive oxygen species (ROS). This study was designed to test whether a polyhydroxylated fullerene derivative [C60(OH)9±2] protects against oxidative stress in cultured RAW 264.7 cells and ischemia-reperfused (IR) lungs. We used sodium nitroprusside (SNP) and H2O2 to elevate nitric oxide and oxidants, respectively, in the culture medium of RAW 264.7 cells. In addition, the experimental procedure for the induction of IR-induced injury of isolated rat lungs was divided into three periods: baseline, ischemia and reperfusion. In RAW 264.7 cells, SNP (1 mM) or H2O2 (400 mM) caused a marked (90%) decrease in cell viability, and this decrease was dose-dependently reversed by pretreatment with C60(OH)9±2 (10 to 50 mM). The increase in ROS production induced by SNP or H2O2 was significantly suppressed by C60(OH)9±2. Also, the decrease in mitochondrial membrane potential induced by SNP or H2O2 was significantly reversed by C60(OH)9±2. However, high concentration of C60(OH)9±2 (1 and 1.5 mM) induced cell death (apoptosis or necrosis). In the isolated rat lung, the increases in pulmonary artery pressure and capillary filtration pressure induced by SNP during IR was significantly reversed by C60(OH)9±2 (10 mg/kg). These results indicate that the polyhydroxylated fullerene derivative C60(OH)9±2 in low concentration can protect against oxidative stress in RAW 264.7 cells and IR lungs.

目錄
圖次…………………………………………………………….…….2
中文摘要……………………………………………………………..9
英文摘要……………………………………………………….…….11
前言…………………………………………………………………..13
材料與方法…………………………………………………………..24
實驗結果……………………………………………………………...31
討論…………………………………………………………………...40
結論…………………………………………………………………...50
參考文獻……………………………………………………………...51
附圖…………………………………………………………………...64

Barazzone C, Horowitz S, Donati YR, Rodriguez I, Piguet PF. Oxygen toxicity in mouse lung: pathways to cell death. Am J Respir Cell Mol Biol 19:573-581, 1998
Becker L, Bada JL, Winans RE, Hunt JE, Bunch TE, French BM. Fullerene in the 1.85-billion-year-old Sudbury impact structure. Science. 265: 642-645, 1994
Becker PM, Pearse DB, Permutt S, Sylvester JT. The separate effects of ischemia and reperfusion on vascular permeability in ventilated ferret lung. J Appl Physiol 73: 2616-2622, 1992
Becker PM, Pearse DB, Sylvester JT. The effects of oxygen tension and glucose concentration on ischemia injury in ventilated ferret lung. J Appl Physiol 75: 1233-1237, 1993
Chen X, Gillis CN. Effect of free radicals on pulmonary vascular response to acetylcholine. J Appl Physiol 71: 821-825, 1991
Cooke JP, Tsao PS. Cytoprotective effects of nitric oxide. Circulation 88: 2451-2454, 1993
Dawson CA, Linehan JH, Rickaby DA. Pulmonary microcirculatory hemodynamics. Ann N Y Acad Sci 384: 90-106, 1982
Dawson VL, Dawson TM, London ED, Bredt DS, Synder SH. Nitric oxide mediates glutamate neurotoxicity in primary cortical culture. Proc Natl Acad Sci USA 88: 6368-6371, 1991
Drake R, Gaar KA, Taylor AE. Estimation of the filtration coefficient of pulmonary exchange vessels. Am J Physiol 234: H266-274, 1978
Dugan LL, Turestsky DM, Du C, Lobner D, Wheeler M, Almi CR, Shen C KF, Luh TY, Choi D, Lin TS. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci USA 94: 9434-9439, 1997
Fisher AB, Dodia C, Tan Z, Ayene I, Eckenhoff RG. Oxygen-dependent lipid peroxidation during lung ischemia. J Clin Invest 88: 674-679, 1991
Fischer K, Andreesen R, Mackensen A. An improved flow cytometric assay for the determination of cytotoxic T lymphocyte activity. J Immunol Meth 259: 159-69, 2002
Fischer S, Maclean AA, Liu M, Gardella JA, Slutsky AS, Suga M, Moreira JFM, Keshavjee S. Dynamic Changes in Apoptotic and Necrotic Cell Death Correlate with Severity of Ischemia-Reperfusion Injury in Lung Transplantation. Am J Respir Crit Care Med 162: 1932-1939, 2000
Freeman BA, Crapo JD. Hyperoxia increases oxygen radical production in rat lung and lung mitochondria. J Biol Chem 256: 10986-10992, 1981
Friedman SH, Decamp DL, Sijbesma RP, Srdanov G, Wudl F, Kenyon GLJ. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J Am Chem Soc 115: 6506-6509, 1993
Furchgott RF, vanhoutte PM. Endothlium-derived relaxing and contracting factors. FASEB J 3: 2007-2018, 1989
Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests a role as intercellular messenger in the brain. Nature 336: 385-387, 1998
Halliwell B. Oxidants and human disease: some new concepts. FASEB J 1: 358-364, 1987
Halmosi R, Berente Z, Osz E, Toth K, Literati-Nagy P, Sumegi B. Effect of Poly(ADP-Ribose) Polymerase Inhibitors on the Ischemia-Reperfusion-Induced Oxidative Cell Damage and Mitochondrial Metabolism in Langendorff Heart Perfusion System. Mol Parmacol 59: 1497-1505, 2001
Heffner JE, Repine JE. Pulmonary strategies of antioxidants defense. Am Rev Respir Dis 140: 531-554, 1989
Hirasawa K, Jun HS, Maeda K, Kawaguchi Y, Itagaki S, Mikami T Baek HS, Doi K, Yoon Jw. Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. J Virol 71: 4024-4031, 1997
Johansson A, Lundborg M, Skold CM, Lundahl J, Tornling G, Eklund A, Camner P. Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages. Am J Respir Cell Mol Biol 16: 582-588, 1997
Jones DR, Becker RM, Hoffmann SC, Lemasters JJ, Egan TM. When does the lung die ? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung. J Appl Physiol 83: 247-252, 1997
Klaassen CD. Casarette and Doull´s Toxicology: The Basic Science of Poisons. Fifth edition, 1995. p. 13-33
Kleemann R, Rothe H, Kolb-Bachofen V, Xie QW, Nathan C, Martin S, Kolb H. Transcription and translation of inducible nitric oxide synthase in pancreas of prediabetic BB rat. FEBS Lett 328: 9-12, 1993
Kroncke KD, Kolb-Bachofen V, Berschick B, Burkart V, Kolb H. Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation. Biochem Biophys Res Commun 175: 752-758, 1991
LeBel CP, Ali SF, McKee M, Bondy SC. Organometal —induced increased in oxygen reactive species: the potential of 2’, 7’-dichlorofluorescin diacetate as an index of neurotoxic damage. Toxicol Appl Pharmacol 104: 17-24, 1990
Li FJ, Kondo T, Zhao QL, Tanabe K, Ogawa R, Li M, Arai Y. Enhancement of hyperthermia-induced apoptosis by free radical initiator, 2, 2-azobis (2-amidinopropane) dihydrochloride, in human histiocytic lymphoma U937 cells. Free Rad Res 35; 281-299, 2001
Lin W, Wei X, Xue H, Kelimu M, Tao R, Song Y, Zhou Z. Mut Res 466: 187-195, 2000
Lu LH, Lee YT, Chen HW, Chiang LY, Huang HC. Huang. The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells. Brit J Pharmacol 123: 1097-1102, 1998
Liu X, Yang CN, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrom c. Cell 86: 147-157, 1996
Maestro D, Bjork RF, Bjork J, Arfors KE. Increase in microvascular permeability induced by enzymatically generated free radiacls.Role of superoxide anion radical, hydrogen peroxide, and hydroxyl radical. Microvasc Res 22: 255-270, 1981
Mauricio D, Mandrup-Poulsen T. Apoptosis and the pathogenesis
of IDDM : a question of life and death. Diabetes 47: 1537-1543, 1998
McCord JM. Oxygen-derived free radicals in post-ischemic tissue
injury. N Engl J Med 312: 159-163, 1985
Meister A, Anderson ME. Glutathion. Annu Rev Biochem 52: 711-760, 1983
Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 329: 2002-2012, 1993
Monti D, Moretti L, Salviolo S, Straface E, Malorni W, Pellicciari R, Schettini G, Bisaglia M, Pincelli C, Fumelli C, Bonafe M, Franceschi C. C60 carboxyfullerene exerts a protective activity against oxidative stress- induced apoptosis in human peripheral blood mononuclear cells. Biochem Biophys Res Commun 277: 711-717, 2000
Nakazawa H, Genka C, Fujishima M. Pathological aspects of active oxygen/free radicals. Jap J Physiol 46: 15-32, 1996
Nathan C, Xie QW. Nitric oxide synthase: Role, tolls and control. Cell 78: 915-918, 1994
Normandin L, Herve P, Brink C, Chapelier AR, Dartevelle PG, Mazmanian GM. L-arginine and pentoxyfylline attenuate endothelial dysfuvtion after lung reperfusion in the rabbit lung. Ann Throac Surg 60: 646-650, 1995
Olesen SP, Clapham DE, Davies PF. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331: 168, 1988
Prokhorova S, Lavnikova N, Laskin DL. Functional characterization of intersititial macrophages and subpopulations of alveolar macrophages from rat lung. J Leuk Biol 55: 141-146, 1994
Rabinovitch A, Suarez-Pinzon WL, Sorensen O, Bleackley RC. Inducible nitric oxide synthase (iNOS) in pancreatic islets of nonobese diabetic mice: identification of iNOS-expressing cells and relationships to cytokines expressed in the islet. Endocrinology 137: 2093-2099, 1996
Reddy S, Yip S, Karanam M, Poole CA, Ross JM. An immunhistochemical study of macrophage influx and the co-localization of inducible nitric oxide synthase in the pancreas of non-obese diabetic (NOD) mice during disease acceleration with cyclophosphamide. Histochem J 31: 303-314, 1999
Rossi F. The O2-forming NADPH Oxidase of phagocytes: nature, mechanisms of activation and function. Biochim Biophys Acta 853: 65-89, 1986
Rothe H, Faust A, Schade U, Kleemann R, Bosse G, Hibino T, Martin S, Kolb H. Cyclophosphamide treatment of female non-obese diabetic mice cause enhancedexpression of inducible nitric oxide synthase and interferon-gamma, but not of interleukin-4. Diabetologia 37: 1154-1158, 1994
Sanders SP, Zweier IL, Kuppusamy P, Zweier JL, Kuppusamy P, Harrison SJ, Bassett DJP, Gabrielson EW, Aust S, RoerigD, Pederson T. Evidence for superoxide generation by NADPH-cytochrom C reductase of rat liver microsome. Biochem Biophys Res Commun 47: 1133-1137, 1972
Sanderud J, Norstein J, Saugstad OD. Reactive oxygen metabolites produce pulmonary vasoconstriction in young pigs. Ped Res 29: 543-547, 1991
Sanderud J, Bjoro K, Saugstad OD. Oxygen radicals stimulate thromboxane and prostacyclin synthesis and induce vasoconstriction in pig lungs. Scand J Clin Lab Invest 53: 447-455, 1993
Sato K, Li J, Metais C, Bianchi C, Sellke F. Increased pulmonary vascularcontraction to serotonine after cadiopulmonarybypass: role of cyclooxygenase. J Surg Res 90: 138-143, 2000
Satoh M, Matsuo K, Kiriya H, Hirobe TM, Takayanagi I. Inhibitory effect of a fullerene derivative, monomalonic acid C60, on nitric oxide-dependent relaxation of aortic smooth muscle. Gen Pharmacol 29: 345-351,1997
Schinazi RF, Sijbesma R, Srdanov G, Hill CL, Wudl F. Synthesis and virucidal activity of a water soluble ,configurationally stable, derivated C60 fullerene. Antimicrob Agents Chemother 37: 1707-1710, 1993
Shepherd JT, Katusic ZS, Verdernikov Y, Vanhoutte PM. Machanisms of coronary vasospasm: role of endothelium. J Mol Cell Cardiol 23 (Suppl 1): 125-131, 1991
Simbula G, Glascott PA, Akita S, Hoek JB, Farber JL. Two mechanisms by which ATP depletion potentiates induction of the mitochondrial permeability transition. Am J Physiol 273: 479-478, 1997
Sijbesma R, Srdanov G, Wudl F, Castoro JA, Wilkens C, Friedman SH, Decamp DL, Kenyon GL. Synthesis of a fullerene derivative for the inhibition of HIV enzymes. J Am Chem Soc 115: 6510-6514, 1993
Susin S, Lorenzo H, Zamzami N, Marzo I, Brenner C, Larochette N, Prevost M, Alzari P, Kroemer G. Mitochondrial release of caspase-2 and -9 during the apoptotic process. J Exp Med 189: 381-393, 1999
Sylvester JT. Hyperoxic sheep pulmonary microvascular endothelial cells generate free radicals via mitochondria electron transport. J Clin Invest 91: 46-52, 1993
Toniolo C, Bianco A, Maggini M, Scorrano G, Prato M, Marastoni M, Tomatis R, Spisani S, Palu G, Blarir EDJ. A bioactive fullerene peptide. J Med Chem 37: 4558-4562, 1994
Uehara T, Kikuchi Y, Nomra Y. Caspase activation accompanying cytochrom c release from mitochondria is possibly involved in nitric oxide-induced neuronal apoptosis in SH-SY5Y cells. J. Neurochem 72: 196-205, 1999
Virag L, Salzman Al, Szabo C. Poly (ADP-Ribose) synthetase activation mediators mitochondrial injury during oxidant-induced cell death. J Immunol 161: 3753-3759, 1998
Walia M, Sormaz L, Samson SE, Lee RM, Grover AK. Grover. Effects of hydrogen peroxide on pig coronary artery endothelium. Eur J Pharmacol 400: 249-253, 2000
Wang W, Xu Z, Lin L, Wang W, Li D, Wang Z. Protective effect of L-arginine on liver during ischemia-reperfusion injury. Chung Hua Kan Tsang Ping Tsa Chih 8: 370-372, 2000
Wolff DJ, Mialkowski K, Richardson CF, Wilson SR. C60-fullerene monomalonate adducts selectively inactivate neuronal nitric oxide synthase by uncoupling the formation of reactive oxygen intermediates from nitric oxide production. Biochemistry 40: 37-45, 2001
Wolff DJ, Papoiu ADP, Mialkowaski K, Richardson CF, Schuster DI, Wilson SR. Inhibition of nitric oxide synthase isoforms by tris-malonyl-C60- Fullerene adducts. Arch Biochem Biophy 378: 216-223, 2000
Yamago S, Tokuyama H, Nakamura E, Kikuchi K, Kananishi S, Sueki K, Nakahara H, Enomoto S, Ambe F. In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol 2: 385-389, 1995
Yoshida K, Yoshimura K, Haniuda M. L-Arginine Inhibits Ischemia-Reperfusion Lung Injury in Rabbits. J Surg Res 85: 9-16, 1999

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 黑豆及其主要成分對α腫瘤壞死因子所誘導人類主動脈內皮細胞發炎反應之影響
2. 日本腦炎病毒造成小鼠不同腦區及脊髓神經元及膠質細胞損傷之機制
3. CCY1a-C1影響巨噬細胞株RAW264.7生成一氧化氮的研究
4. 3-methylquercetin抑制Raw264.7細胞中nitricoxide表現和抑制人類非小細胞肺癌(H-460)生長的機制
5. 緩激汰、肥大細胞和活性氧物種在吸入噴霧性檸檬酸導致天竺鼠氣管道收縮之角色
6. 脂肪酸及過氧化氫對大鼠心肌細胞中粒線體內鈣、鈉離子濃度之影響
7. 人類血管收縮素元基因啟動子多型性C(-532)T對其基因基礎轉錄之影響及其與人類心血管疾病之關係
8. 泌乳素在田鼠黃體促進作用上之角色
9. 過度糖化最終產物在RAW264.7細胞誘導iNOS表現中蛋白質激脢C所扮演的角色
10. 第一部份:核酸內解脢抑制劑aurintricarboxylicacid影響內毒素引發iNOS基因誘導作用之機轉研究;第二部份:15dPGJ2在RAW264.7巨噬細胞株及Hep3B肝臟腫瘤細胞株中造成細胞凋亡之機轉
11. 纖維母細胞生長因子及其受體訊號在果蠅視覺系統誘導氣管延長
12. 探討藥用真菌及蝸牛分泌液之美白、修復及抗發炎機制
13. 休止期纖維母細胞比增生期纖維母細胞具有更強的發炎反應
14. 介白素-1第二型受器促進人類血管內皮細胞和人類纖維母細胞之生物活性
15. CD93蛋白在血管內皮細胞發炎上之功能探討
 
系統版面圖檔 系統版面圖檔