臺灣博碩士論文加值系統

背景與目的：缺血性心臟病是目前全球死亡率第一名的疾病。冠狀動脈缺血會引起心肌受損，甚至影響心臟的收縮功能，最後導致心臟收縮不協同和左心室射出率的異常。血栓是造成缺血性心臟病的主因，因此血小板扮演重要的角色，而血小板的活化則是會受到粒線體所調控。研究顯示較高的心肺適能會降低心血管疾病死亡率的相對風險，普遍認為規律的運動對於健康是有好處的，但最佳的運動模式其實還沒有被定義出來。相較於運動時間，運動的強度對於心臟的益處是影響較大的。有氧間隔式運動訓練(aerobic interval training, AIT)是由高強度運動中間穿插動態的恢復期，相較於連續中等運動訓練(moderate continue training, MCT)，AIT更能促進最大攝氧量和心臟重塑、增加心臟功能。另外也有研究有發現運動訓練可以改善心肌梗塞後大鼠心肌的粒線體功能、降低血小板的活性。因此本研究想探討MCT與AIT對於血小板粒線體功能，以及左心室心臟動力學的改變。實驗方法：收取46位20~28歲的坐式生活健康年輕男性，隨機分派為控制組(無運動訓練)10位，及運動訓練組36位。運動訓練組再隨機分為有氧間隔性運動訓練( AIT，最大攝氧量之40%及80%交替間隔五回，30分鐘/天，5天/週，連續6週)與中度持續性運動訓練( MCT，60 %最大攝氧量持續30分鐘/天，5天/週，連續6週)。運動訓練前後，皆會進行最大運動測試、低氧運動測試，以及常氧和低氧心臟超音波測試，並在最大運動與低氧運動測試前及結束後立即收集血液樣本，用於血小板粒線體功能及凝血酶生成之實驗。結果：經過六週後AIT組與MCT組的最大運動能力皆有顯著進步。兩種運動模式也能鈍化因為低氧造成的凝血酶生成速率和單位時間生成量的增加。另外，AIT運動訓練顯著的增加左心室功能，包括舒張末期容積、左心室射出率、心輸出量、心臟做功量，同時還會降低SDI與DDI。AIT運動還可以增加血小板粒線體ATP-linked和ETS的耗氧速率，但沒辦法完全鈍化因為運動測試造成的耗氧速率降低。結論：兩種運動模式皆可以促進心肺適能，還可以減緩因為低氧造成的凝血酶增加。另外，AIT訓練可以大幅的促進左心室功能以及增加血小板粒線體功能。

Background: Ischemic heart disease is the leading cause of death in the world. Ischemia induced cardiac muscle damage would affect the contraction and myocardial synergy. Besides, left ventricular dysfunction leads to less ejection fraction and higher systolic dyssynchrony index. Thrombosis is the main cause to cardiac ischemia It is well recognized that platelets mitochondria regulate the cell function and play a key role in arterial thrombosis. Nutrient oxidation provides the substrates for mitochondrial electron transport and pumping protons into the intermembrane space. The proton gradient difference between mitochondrial inner membrane and intermembrane space generate the mitochondrial membrane potential and proton motive force, which is essential for ATP synthesis. The mitochondrial membrane potential also positively regulates calcium uptake as well as mitochondrial ROS production. Mitochondrial ROS and high calcium concentration promote the formation of mitochondrial permeability transition pore, which mediates both platelet activation and apoptosis. Activated platelets may clump together to form thrombus. Exercise intensity, rather than duration, is the key factor in determining cardiac benefits. Aerobic interval training (AIT) consists of bouts of high-intensity exercise separated by active recovery phases, which may improve lactic acid removing from working muscles and prolong the tolerable exercise time. Some research showed that AIT had greater improvement in VO2max and cardiac remodeling than moderate continue training (MCT). The purpose of this study is to investigate the effects of AIT and MCT on mitochondrial oxidative phosphorylation and LV function of platelets. Methods: Forty-six sedentary males were randomized to to control group (n=10) or perform perform either AIT (3-minute intervals at 40% and 80%VO2max, n=18) or MCT (sustained 60%VO2max, n=18) for 30 minutes/day, 5 days/week for 6 weeks. The pre-test and post-test measurements include mitochondrial function, analyzed by a high resolution respirometer (Oxygraph-2k), and LV function, analyzed by 3D echocardiography. Result: Both AIT and MCT groups had improvement in maximal exercise performance. Also, both protocols could alleviate the peak height and generation rate of thrombin which were increased due to hypoxia exercise test. In addition, AIT could improve in muscle mass, EF, SV, CO, synergy and cardiac power of left ventricular. After training, the OCR of ATP-linked and ETS were improved in AIT group in resting, but were not changed in MCT group. However, the trend of decrease was the same after training in both groups. Conclusion: This two exercise protocols exhibits similar improvement in cardiopulmonary fitness. Otherwise, both protocols could alleviate the thrombin generation which were increased due to hypoxia. In addition, AIT could improve more left ventricular function. Also, AIT improved substrate dependent mitochondrial function in resting, but not after exercise tests. Therefore, AIT is a more effective exercise for improving LV and platelets mitochondrial functions.

指導教授推薦書
口試委員會審定書
致謝 iii
中文摘要 v
英文摘要 vii
第一章 緒論 - 1 -
1.1 研究背景及目的 - 1 -
1.2 研究假設 - 4 -
第二章 文獻回顧 - 5 -
2.1 血小板與血栓形成 - 5 -
2.2 血小板與粒線體 - 10 -
2.3 血小板、粒線體與疾病 - 12 -
2.4 運動與心肺適能 - 14 -
2.5 運動對於血小板以及粒線體的影響 - 19 -
第三章 實驗設計 - 21 -
3.1. 實驗材料 - 21 -
3.1.1. 試劑 - 21 -
3.1.2. 儀器 - 24 -
3.2. 研究方法 - 27 -
3.2.1. 受測者招募 - 27 -
3.2.2. 實驗流程 - 27 -
3.2.3. 運動訓練 - 33 -
3.2.4. 血液實驗 - 33 -
3.3. 統計分析 - 38 -
第四章 實驗結果 39
4.1. 受試者基本資料 39
4.2. 運動訓練對運動表現之影響 40
4.3. 運動訓練對於常氧下左心室功能之影響 42
4.4. 運動訓練對於低氧下左心室功能之影響 45
4.5. 粒線體對凝血酶生成之影響 46
4.6. 運動對於凝血酶生成之影響 48
4.7. 最大運動測試與AIT及MCT訓練對內源性血小板粒線體功能之影響 52
4.8. 最大運動測試與AIT及MCT訓練對通透性血小板粒線體功能之影響 54
4.9. 低氧運動測試與AIT及MCT訓練對內緣內源性血小板粒線體功能之影響 55
4.10. 低氧運動測試與AIT及MCT訓練對通透性血小板粒線體功能之影響 56
第五章 討論 58
5.1. 運動對於左心室功能之影響 58
5.2. 運動訓練後凝血酶產生量的下降 60
5.3. 運動訓練影響粒線體功能 60
5.4. 研究限制 62
第六章 結論 63
參考資料 64
圖表 73
附錄 107

圖目錄
圖 一 實驗流程圖 75
圖 二 運動訓練模式 76
圖 三 常氧運動超音波下三組之心跳、心搏量、心輸出量變化 77
圖 四 常氧心臟超音波下三組之左心室舒張末期容積與收縮末期容積之變化，及左心室射出率和心臟做功量之變化 78
圖 五 常氧心臟超音波下三組之左心室體積與速度層面的收縮協同性變化 79
圖 六 常氧心臟超音波下三組之左心室體積與速度層面的舒張協同性變化 80
圖 七 低氧心臟超音波下三組之心跳、心搏量、心輸出量變化 87
圖 八 低氧心臟超音波下三組之左心室舒張末期容積與收縮末期容積之變化，及左心室射出率和心臟做功量之變化 88
圖 九 低氧心臟超音波下三組之左心室體積與速度層面的收縮協同性變化 89
圖 十 低氧心臟超音波下三組之左心室體積與速度層面的舒張協同性變化 90
圖 十一 常氧運動超音波下AIT組之左心室各層舒張末期容積與收縮末期容積及心搏量之變化 81
圖 十二 常氧運動超音波下AIT組之左心室各層cardiac power之變化 82
圖 十三 常氧運動超音波下AIT組之左心室各層體積與速度層面的收縮協同性變化 83
圖 十四 常氧運動超音波下AIT組之左心室各層體積與速度層面的舒張協同性變化 84
圖十五 最大運動測試與AIT及MCT訓練對內源性血小板粒線體功能之影響 99
圖十六 最大運動測試與AIT及MCT訓練對通透性血小板粒線體功能與BHI之影響 101
圖十七 低氧運動測試與AIT及MCT訓練對內源性血小板粒線體功能之影響 103
圖十八 最大運動測試與AIT及MCT訓練對通透性血小板粒線體功能與BHI之影響 105
圖 十九 抑制劑對於凝血酶生成的各個參數之影響 91
圖 二十 流式細胞儀測得粒線體內超氧化物與血小板表面磷脂絲胺酸(PS)之結果 92
圖 二十一 加入穀胱甘肽與FCCP對凝血酶生成之影響 93
圖 二十二 運動訓練對凝血酶開始生成的時間之影響 94
圖 二十三 運動訓練對總時間內所生成的總凝血酶數量之影響 95
圖 二十四 運動訓練對凝血酶生成之最大量的影響 96
圖 二十五 運動訓練對凝血酶生成最大量的時間之影響 97
圖 二十六 運動訓練影響凝血酶開始生成時與生成最大量時之間的斜率 98

表目錄
表一 人體基本測量數值 73
表二 運動測試表現 74

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