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研究生:吳凡妮
研究生(外文):Fan-Ni Wu
論文名稱:運動訓練對於高血壓及糖尿病老鼠心臟凋亡與存活訊息途徑的影響
論文名稱(外文):EFFECT OF EXERCISE TRAINING ON CARDIAC APOPTOTIC AND SURVIVAL PATHWAYS IN HYPERTENSIVE AND DIABETIC RATS
指導教授:林子恩林子恩引用關係
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:基礎醫學研究所
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:2009
畢業學年度:97
語文別:英文
論文頁數:125
中文關鍵詞:糖尿病高血壓運動凋亡
外文關鍵詞:diabeteshypertensionexerciseapoptosis
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隨著目前國人代謝症候群發生機率的增加,並且發現心臟方面的併發症致死率在高血壓及糖尿病病人中佔有極大的比例。許多研究中認為高血壓和糖尿病引起的心臟病變和心肌細胞的凋亡有關,但確切相關路徑的研究探討卻是非常有限。大多數的研究著重於心臟收縮等功能,在本篇實驗中,我們將細部去討論心肌細胞的訊息傳遞路徑的改變。另外當使用運動做為一治療方法,是否能對於心臟相關的訊息傳遞路徑有所影響。文中利用先天性高血壓老鼠(SHR)和糖尿病鼠(DM),糖尿病鼠是利用streptozotocin破壞β細胞使胰島素無法分泌而使血糖升高,進而誘導致病。隨後再將這些高血壓和糖尿病老鼠進一步的分組,分為非運動組(SHR and DM)和運動組(SHR-EX and DM-EX)。運動訓練每周五天,每天一小時,分別訓練十二周和八周。對照組分別為Wistar Kyoto rats (WKY)和Wistar rats (Control)。最後在運動訓練過程結束後,利用H&E stain和TUNEL和 western blotting的實驗來觀察心肌細胞組織間和蛋白質間的變化。心肌細胞凋亡路徑包括death-dependent和mitochondria-dependent 路徑。不論是在高血壓(SHR)或是糖尿病(DM)的組別中,心肌細胞凋亡路徑的蛋白質表現量和對照組(WKY and Control)相比較皆有顯著的上升。而運動訓練後的組別(SHR-EX and DM-EX),相較於沒有運動的高血壓及糖尿病組(SHR and DM),凋亡相關路徑蛋白質表現量皆明顯下降。而在survival訊息傳遞路徑中蛋白質的表現量,高血壓和糖尿病的組別(SHR and DM)明顯的比對照組(WKY and Control)低。而在運動訓練之後,蛋白質的表現量皆有明顯的上升。在高血壓及糖尿病的實驗中發現,運動訓練可有效的抑制心肌細胞凋亡相關蛋白的表現,並且促進survival的相關蛋白表現量,成功的保護了心肌細胞免於走向細胞凋亡的途徑。因此本篇的實驗發現運動可提供高血壓和糖尿病病人一個有效的預防心臟方面的併發症的發生。
The metabolic syndrome is a major risk factor and it raised the mortality in recently years. This study focuses on the hypertension and diabetes. Both these two diseases caused the heart failure in the end. In the reviews, cardiac apoptosis was found in hypertension and diabetes, but very limited information regarding the effects of exercise training on cardiac apoptosis in hypertension and diabetes was available. The purpose of this study was to evaluate the therapeutic effects of exercise training on hypertension and diabetes related cardiac apoptosis. Spontaneously hypertensive rats and streptozotocin-induced diabetic rats were divided into sedentary group (SHR and DM) and unwanted running exercise on treadmill 1 hour daily, 5 sections per week, for 12 and 8 weeks (SHR-EX and DM-EX). Wistar Kyoto rats (WKY) and Wistar rats (Control) as a negative control. After exercise training or sedentary status, the excised hearts were measured by H&E stain, TUNEL assay and western blotting. Protein levels of apoptotic pathway, including death and mitochondria dependent pathways, were increased in both SHR and DM groups; and survival related proteins were decreased in both SHR and DM groups compared with normal groups (WKY and Control). Cardiac mitochondria and death receptor dependent apoptotic pathway were decreased and survival pathway was increased in both SHR-EX and DM-EX groups compared with normal groups (WKY and Control). Exercise training might suppress cardiac apoptotic pathways and elevated cardiac survival pathway in hypertensive and diabetic rat models. The findings may provide one of the possible therapeutic approaches for preventing cardiac apoptosis in hypertension and diabetes.
Part 1
Effect of exercise training on cardiac fas dependent apoptosis in spontaneously hypertensive rats 1
Introduction 3
Materials and Methods 5
Results 8
Discussion 10
References 13
Figures 16


Part 2
Effect of exercise training on cardiac mitochondria dependent apoptosis in spontaneously hypertensive rats 25
Introduction 27
Materials and Methods 29
Results 32
Discussion 34
References 37
Figures 40


Part 3
Effect of exercise training on cardiac survival pathway in spontaneously hypertensive rats 50
Introduction 52
Materials and Methods 54
Results 57
Discussion 59
References 62
Figures 65


Part 4
Effect of exercise training on cardiac apoptotic pathway in streptozotocin-induced diabetic rats 74
Introduction 76
Materials and Methods 79
Results 83
Discussion 85
References 88
Figures 91


Part 5
Effect of exercise training on cardiac survival pathway in streptozotocin-induced diabetic rats 103
Introduction 105
Materials and Methods107
Results 111
Discussion 113
References 115
Figures 118
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