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標題: | oxfenicine對streptozotocin所引發之糖尿病鼠其動脈系統
物理性質的影響 Effects of oxfenicine on the mechanical properties of the arterial system in streptozotocin-induced diabetic rats |
作者: | Cheng-Yu Shih 石振宇 |
指導教授: | 張國柱(Kuo-Chu Chang) |
關鍵字: | 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, carnitine palmitoyltransferase-I,oxfenicine,fatty acid oxidation,STZ-induced diabetic rats,free fatty acids,aortic input impedance analysis,total peripheral resistance, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42675 |
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