請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42675
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 張國柱(Kuo-Chu Chang) | |
dc.contributor.author | Cheng-Yu Shih | en |
dc.contributor.author | 石振宇 | zh_TW |
dc.date.accessioned | 2021-06-15T01:19:26Z | - |
dc.date.available | 2010-09-15 | |
dc.date.copyright | 2009-09-15 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-27 | |
dc.identifier.citation | Bachmann, E. and E. Weber (1988). 'Biochemical mechanisms of oxfenicine cardiotoxicity.' Pharmacology 36(4): 238-48.
Bardell, A. L. and K. M. MacLeod (2001). 'Evidence for inducible nitric-oxide synthase expression and activity in vascular smooth muscle of streptozotocin-diabetic rats.' J Pharmacol Exp Ther 296(2): 252-9. Bays, H. E. (2009). ''Sick fat,' metabolic disease, and atherosclerosis.' Am J Med 122(1 Suppl): S26-37. Bergman, G., L. Atkinson, J. Metcalfe, N. Jackson and D. E. Jewitt (1980). 'Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris.' Eur Heart J 1(4): 247-53. Brownlee, M. (2005). 'The pathobiology of diabetic complications: a unifying mechanism.' Diabetes 54(6): 1615-25. Burattini, R., S. Fioretti and L. Jetto (1985). 'A simple algorithm for defining the mean cardiac cycle of aortic flow and pressure during steady state.' Comput Biomed Res 18: 303-312. Chandler, M. P., P. N. Chavez, T. A. McElfresh, H. Huang, C. S. Harmon and W. C. Stanley (2003). 'Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia.' Cardiovasc Res 59(1): 143-51. Chang, K. C., K. L. Hsu, C. D. Tseng, Y. D. Lin, Y. L. Cho and Y. Z. Tseng (2006). 'Aminoguanidine prevents arterial stiffening and cardiac hypertrophy in streptozotocin-induced diabetes in rats.' Br J Pharmacol 147(8): 944-50. Chang, K. C., K. L. Hsu and Y. Z. Tseng (2003). 'Effects of diabetes and gender on mechanical properties of the arterial system in rats: aortic impedance analysis.' Exp Biol Med (Maywood) 228(1): 70-8. Creager, M. A., T. F. Luscher, F. Cosentino and J. A. Beckman (2003). 'Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I.' Circulation 108(12): 1527-32. Deshpande, A. D., M. Harris-Hayes and M. Schootman (2008). 'Epidemiology of diabetes and diabetes-related complications.' Phys Ther 88(11): 1254-64. Di Marzio, D., A. Mohn, Z. H. Mokini, C. Giannini and F. Chiarelli (2006). 'Macroangiopathy in adults and children with diabetes: from molecular mechanisms to vascular damage (part 1).' Horm Metab Res 38(11): 691-705. Dincer, U. D., A. Onay, N. Ari, A. T. Ozcelikay and V. M. Altan (1998). 'The effects of diabetes on beta-adrenoceptor mediated responsiveness of human and rat atria.' Diabetes Res Clin Pract 40(2): 113-22. Drake-Holland, A. J. and J. E. Passingham (1983). 'The effect of Oxfenicine on cardiac carbohydrate metabolism in intact dogs.' Basic Res Cardiol 78(1): 19-27. Du, X., D. Edelstein, S. Obici, N. Higham, M. H. Zou and M. Brownlee (2006). 'Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation.' J Clin Invest 116(4): 1071-80. Foley, J. E. (1992). 'Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus.' Diabetes Care 15(6): 773-84. Greaves, P., J. Martin, M. C. Michel and P. Mompon (1984). 'Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism.' Arch Toxicol Suppl 7: 488-93. Higgins, A. J., M. Morville, R. A. Burges, D. G. Gardiner, M. G. Page and K. J. Blackburn (1980). 'Oxfenicine diverts rat muscle metabolism from fatty acid to carbohydrate oxidation and protects the ischaemic rat heart.' Life Sci 27(11): 963-70. Howarth, F. C. and M. A. Qureshi (2006). 'Effects of carbenoxolone on heart rhythm, contractility and intracellular calcium in streptozotocin-induced diabetic rat.' Mol Cell Biochem 289(1-2): 21-9. Kahles, H., W. Schafer, T. Lick, J. Junggeburth and K. Kochsiek (1986). 'Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine.' Basic Res Cardiol 81(3): 258-66. Kannel, W. B. and D. L. McGee (1979). 'Diabetes and cardiovascular disease. The Framingham study.' JAMA 241(19): 2035-8. Kashiwagi, A. (1995). 'Rationale and hurdles of inhibitors of hepatic gluconeogenesis in treatment of diabetes mellitus.' Diabetes Res Clin Pract 28 Suppl: S195-200. Kato, K., D. C. Chapman, H. Rupp, A. Lukas and N. S. Dhalla (1999). 'Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats.' J Appl Physiol 86(3): 812-8. Korb, H., A. Hoeft, D. H. Hunneman, R. Schraeder, H. G. Wolpers, W. Wober and G. Hellige (1984). 'Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(S)-4-hydroxyphenylglycine].' Naunyn Schmiedebergs Arch Pharmacol 327(1): 70-4. Laxminarayan, S., P. Sipkema and N. Westerhof (1978). 'Characterization of the arterial system in the time-domain.' IEEE Trans Piomed Eng 25: 177-184. Liedtke, A. J. (1981). 'Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart.' Prog Cardiovasc Dis 23(5): 321-36. Liu, Z., K. Brin and F. Yin (1986). 'Estimation of total arterier compliance: an improved method and evaluation of current methods.' Am J Physiol 251: H588-H600. Lopaschuk, G. D., R. B. Wambolt and R. L. Barr (1993). 'An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts.' J Pharmacol Exp Ther 264(1): 135-44. Maeda, C. Y., T. G. Fernandes, H. B. Timm and M. C. Irigoyen (1995). 'Autonomic dysfunction in short-term experimental diabetes.' Hypertension 26(6 Pt 2): 1100-4. Mansford, K. R. and L. Opie (1968). 'Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan.' Lancet 1(7544): 670-1. McGarry, J. D. and D. W. Foster (1980). 'Regulation of hepatic fatty acid oxidation and ketone body production.' Annu Rev Biochem 49: 395-420. Mengi, S. A. and N. S. Dhalla (2004). 'Carnitine palmitoyltransferase-I, a new target for the treatment of heart failure: perspectives on a shift in myocardial metabolism as a therapeutic intervention.' Am J Cardiovasc Drugs 4(4): 201-9. Milnor, W. (1989). 'Hemodynamics, 2nd ed.' Williams and wilkins, Baltimore. Milnor, W. R. (1975). 'Arterial impedance as ventricular afterload.' Circ Res 36(5): 565-70. Mitchell, G., M. Pfeffer, N. Westeshof and J. Pfeffer (1994). 'Measurement of aortic imput impedance in rats.' Am J Physiol 267: H1907-H1915. Nichols, W., C. Conti and W. Walker (1977). 'input impedance of the systemic circulation in man.' Circ Res 40: 451-460. Nichols, W., C. Pepine and E. Geiser (1980). 'Vascular load defined by the aortic input impedance spectrum.' Fed Proc 39: 196-210. Nichols, W. W. and M. F. O'Rourke (2005). 'McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles '. Nielsen, F., B. B. Mikkelsen, J. B. Nielsen, H. R. Andersen and P. Grandjean (1997). 'Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors.' Clin Chem 43(7): 1209-14. Noble, M., I. Gade and D. Frenchard (1976). 'Blood pressure and flow in the ascending aorta of conscious dogs.' Cardiovasc Res 1: 9-21. Peng, Y. I. and K. C. Chang (2000). 'Acute effects of methoxamine on left ventricular-arterial coupling in streptozotocin-diabetic rats: a pressure-volume analysis.' Can J Physiol Pharmacol 78(5): 415-22. Penpargkul, S., F. Fein, E. H. Sonnenblick and J. Scheuer (1981). 'Depressed cardiac sarcoplasmic reticular function from diabetic rats.' J Mol Cell Cardiol 13(3): 303-9. Pepine, C. J. and W. W. Nichols (1982). 'Aortic input impedance in cardiovascular disease.' Prog Cardiovasc Dis 24(4): 307-18. Ross, J., J. Covell, E. Sonnenbuck and E. Braunwald (1966). 'contractiloe state of the heart charecterized by force-velocity relations in variable afterload and isovolumic beats.' Circ Res 18: 149-163. Rother, K. I. (2007). 'Diabetes treatment--bridging the divide.' N Engl J Med 356(15): 1499-501. Schaan, B. D., C. Y. Maeda, H. B. Timm, S. Medeiros, R. S. Moraes, E. Ferlin, T. G. Fernandes, J. P. Ribeiro, H. Schmid and M. C. Irigoyen (1997). 'Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin.' Braz J Med Biol Res 30(9): 1081-6. Schalkwijk, C. G. and C. D. Stehouwer (2005). 'Vascular complications in diabetes mellitus: the role of endothelial dysfunction.' Clin Sci (Lond) 109(2): 143-59. Schmitz, F. J., P. Rosen and H. Reinauer (1995). 'Improvement of myocardial function and metabolism in diabetic rats by the carnitine palmitoyl transferase inhibitor Etomoxir.' Horm Metab Res 27(12): 515-22. Schnedl, W. J., S. Ferber, J. H. Johnson and C. B. Newgard (1994). 'STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells.' Diabetes 43(11): 1326-33. Silan, C. (2008). 'The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats.' Biol Pharm Bull 31(5): 897-902. Sixpkema, P., N. Westerhof and O. Randall (1980). 'The arterial system characterized in the time domain.' Cardiovas Res 14: 270-279. Sniderman, A. D., T. Scantlebury and K. Cianflone (2001). 'Hypertriglyceridemic hyperapob: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus.' Ann Intern Med 135(6): 447-59. Stephens, T. W., A. J. Higgins, G. A. Cook and R. A. Harris (1985). 'Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine.' Biochem J 227(2): 651-60. Stirban, A., P. Rosen and D. Tschoepe (2008). 'Complications of type 1 diabetes: new molecular findings.' Mt Sinai J Med 75(4): 328-51. Szwed, H. (2005). 'The place of metabolic treatment ' heart and metabolism 27: 11-15. Turcani, M. and H. Rupp (1999). 'Modification of left ventricular hypertrophy by chronic etomixir treatment.' Br J Pharmacol 126(2): 501-7. Wang, Z. and H. Gleichmann (1998). 'GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice.' Diabetes 47(1): 50-6. Westerhof, N., P. Sipkema, G. van den Bos and G. Elzinga (1972). 'Forward and backward waves in the arterial system.' Cardiovasc Res 6(6): 648-656. Winer, N. and J. R. Sowers (2004). 'Epidemiology of diabetes.' J Clin Pharmacol 44(4): 397-405. Yagi, K. (1998). 'Simple assay for the level of total lipid peroxides in serum or plasma.' Methods Mol Biol 108: 101-6. Zatz, R. and B. M. Brenner (1986). 'Pathogenesis of diabetic microangiopathy. The hemodynamic view.' Am J Med 80(3): 443-53. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42675 | - |
dc.description.abstract | 目的: 糖尿病患者心臟的葡萄糖以及脂肪酸代謝會出現異常變化,損害心血管系統的功能表現。oxfenicine (OXF) 是一種對carnitine palmitoyltransferase-I (CPT-I) 的抑制劑,可以部分抑制長鏈游離脂肪酸的氧化,已證實對治療糖尿病引發的心臟疾病是有助益的。然而關於長期利用OXF來抑制CPT-I,會對糖尿病患者血管系統造成何種影響的研究相當缺乏。因此,我們利用阻抗頻譜分析方法,來評估OXF是否會在streptozotocin (STZ) 誘發的糖尿病大鼠身上,對其動脈管物理特性造成影響。
方法: 將兩個月大的雄性Wistar大鼠隨機分成四組,分別為 (i) 正常組 (NC);(ii)正常餵予OXF組 (NCOXF);(iii) 糖尿病組 (DM);(iv) 糖尿病餵予OXF組 (DMOXF),先以尾靜脈注射STZ (55mg.kg-1) 來誘發大鼠產生糖尿病,等到其引發出高血糖的症狀後,給予餵藥組大老鼠每天灌食OXF (150mg.kg-1),連續給藥八周並與同齡未給藥的糖尿病控制組做對照。同步記錄大鼠主動脈血壓與血流訊號,用以評估動脈系統的物理特性以及脈波反射現象。實驗後採集血液樣本進行血漿中三酸甘油脂與游離脂肪酸含量的分析。 結果: 經長期餵食糖尿病鼠OXF,發現會造成其主動脈平均血壓值升高以及心輸出量有下降現象,並造成了周邊總阻力百分之三十點五的顯著升高 (P<0.001)。OXF會使得糖尿病鼠血漿中升高的三酸甘油脂以及游離脂肪酸濃度進一步的再升高;血漿中升高的游離脂肪酸有抑制一氧化氮的可能性,導致血管平滑肌張力的上升,相較之下OXF不會對特徵阻抗、波傳輸時間以及波反射係數等動脈血流的脈態性質造成影響。研究結果顯示長期給予OXF抑制糖尿病鼠的CPT-I,無法防止糖尿病所引發的動脈硬化。除此之外,左心室重量對體重的比值不會因為OXF的治療而改變,這意謂著OXF在注射了STZ的大鼠身上不會影響因糖尿病而導致的心臟肥厚現象。 結論: 長時間給予OXF治療以STZ引發的糖尿病大鼠,會造成在周邊循環系統中,血流阻力出現惡化,並增加血漿中三酸甘油脂以及游離脂肪酸的含量。 | zh_TW |
dc.description.abstract | Objective: Changes in metabolism of glucose and fatty acids are reported in the diabetic heart, impairing the performance of cardiovascular system. It has been shown that partial inhibition of long-chain free fatty acid oxidation by oxfenicine (OXF), a carnitine palmitoyltransferase-I (CPT-I) inhibitor, prove beneficial for the treatment of heart disease. However, there are few reports discussing about prolonged inhibition of CPT-I with OXF would cause what kinds of effects on diabetic arterial system. Herein, we determine the effects of OXF on physical properties of the arterial system in STZ-induced diabetic rats, using aortic input impedance analysis..
Methods: Male Wistar rats at 2 months were randomly divided into four groups: (i) normal control (NC); (ii) NC treated with OXF (NCOXF) ; (iii) STZ-diabetic rats (DM); (iv) DM treated with OXF (DMOXF). Diabetes was induced in animals by a single tail vein injection with 55 mg.kg-1 STZ . After induction of hyperglycemia, rats were treated with OXF (150 mg.kg-1) by oral gavage for 8 weeks and compared with the age-matched untreated diabetic controls. Pulsatile aortic pressure and flow signals were measured to describe the physical properties of arterial system along with the pulse wave reflection phenomena. Blood samples were collected after experiment then plasma triglycerides and free fatty acids were analyzed. Results:Long-term administration of OXF to the diabetic rats caused an increase in mean aortic pressure and a decrease in cardiac output, resulting in a significant elevation of 30.5% in total peripheral resistance (P<0.001). OXF further increased the concentrations of plasma triglycerides and free fatty acids that were already higher in diabetic animals. The elevated free fatty acids in plasma have the potential to quench nitric oxide, leading to a rise in vascular smooth muscle tone. By contrast, OXF did not affect the pulsatile nature of blood flows in arteries in terms of aortic characteristic impedance, wave transit time as well as wave reflection factor. These indicated that chronic inhibition of CPT-I with OXF in rats produces no beneficial effect on prevention of the diabetes-induced arterial stiffening. In addition, ratio of the left ventricular weight to body weight remained unchanged by OXF therapy, suggesting that OXF might not change the diabetes-derive cardiac hypertrophy in the animals administered STZ. Conclusion: Prolonged treatment of the STZ-diabetic rats with OXF causes deterioration in resistance to blood flows in peripheral circulation associated with an increase in levels of plasma triglycerides and free fatty acids. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T01:19:26Z (GMT). No. of bitstreams: 1 ntu-98-R95441012-1.pdf: 578211 bytes, checksum: f5558156b6eac3097646c8c859adb180 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 口試委員會審定書i
縮寫名詞對照表iv 中文摘要vi 英文摘要viii 表次x 圖次x 文獻回顧1 糖尿病簡介1 糖尿病引發的血管併發症2 糖尿病對心臟的影響5 carnitine palmitoyltransferase I 抑制劑簡介6 oxfenicine..8 streptozotocin引發之糖尿病動物模型9 動脈物理性質之量化..10 主動脈輸入阻抗頻譜的特性與功能11 研究目的14 材料與方法.15 實驗動物製備15 實驗動物分組15 實驗儀器介紹16 實驗流程.17 左心室比率19 資料轉換與分析方法..19 一、 平均週期運算法則 (mean cycle algorithm).19 二、 時序校正 (timing correction)20 三、 血行力學參數之計算與分析21 生化物質的檢測25 一、 游離脂肪酸的檢測25 二、 三酸甘油脂的檢測26 三、 丙二醛的檢測26 統計方法.27 結果28 基本資料.28 穩態血行力學參數28 脈態血行力學參數29 生化物質.30 討論32 糖尿病及餵食OXF對血漿生化物質方面之影響32 糖尿病及餵食OXF對動脈系統物理特性之影響34 一、 穩態參數方面34 二、 脈態參數方面37 實驗限制.40 結論42 參考文獻48 | |
dc.language.iso | zh-TW | |
dc.title | oxfenicine對streptozotocin所引發之糖尿病鼠其動脈系統
物理性質的影響 | zh_TW |
dc.title | Effects of oxfenicine on the mechanical properties of the arterial system in streptozotocin-induced diabetic rats | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳朝峰(Chau-Fong Chen),賴凌平(Ling-Ping Lai) | |
dc.subject.keyword | 肉鹼棕櫚醯基轉移酶,I,oxfenicine,脂肪酸氧化,STZ所引發之糖尿病鼠,游離脂肪酸,主動脈輸入阻抗頻譜分析,周邊總阻力, | zh_TW |
dc.subject.keyword | carnitine palmitoyltransferase-I,oxfenicine,fatty acid oxidation,STZ-induced diabetic rats,free fatty acids,aortic input impedance analysis,total peripheral resistance, | en |
dc.relation.page | 52 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-07-27 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-98-1.pdf 目前未授權公開取用 | 564.66 kB | 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。