臺灣博碩士論文加值系統

運動的強度 (intensity) 與持續時間 (duration) 強烈影響我們的生理反應。高強度運動 (85 % VO2max) 後，由於活性氧 (Reactive Oxygen Species, ROS) 生成量的大量增加，造成體內氧化物與抗氧化物之間的不平衡，形成所謂的「氧化壓力」。氧化壓力會導致免疫細胞程式性死亡 (programmed cell death)，也就是凋亡 (apoptosis)。但高強度運動後所發生的apoptosis是否由氧化壓力所引發，而其活化凋亡途徑與機制為何，目前尚無研究證實。本研究的目的在於探討連續三天以85 % VO2max的強度進行有氧運動訓練後，所產生的氧化壓力對白血球細胞計劃性死亡的影響。本研究以12名長跑選手為受試對象，平均年齡為22.8 ± 2.39歲；實驗期間施以受試者連續3天，每天30分鐘，85 % VO2max運動強度的原地跑步訓練，分別於第一天跑前 (D1)、第一天跑後 (D1’)、 第三天跑前 (D3)、 第三天跑後 (D3’) 、第五天 (D5) 及第七天 (D7) 採集受試者20毫升靜脈血，以流式細胞儀分析白血球氧化壓力與細胞凋亡，並以反轉錄聚合酶反應 (RT-PCR) 及西方點墨法 (Western blotting) 分析各活化途徑基因與蛋白質之表現。研究結果發現，受試者在連續三天的高強度運動訓練後，白血球中NO與H2O2等活性氧含量顯著增加 (p＜.001)，並造成細胞內GSH的耗空，導致氧化壓力的生成。對週邊血液單核球 (PBMC) 而言，高強度運動後粒線體膜電位 (△Ψm) 顯著下降 (p＜.001)，以及藉由cytochrome c從粒線體中釋放到細胞質中，導致細胞內相關caspase的活化，是運動影響PBMC使進行apoptosis的關鍵之一。而高強度運動對多形核白血球 (PMN) 的影響，除△Ψm的顯著下降 (p＜.001) 和cytochrome c釋放到細胞質之外，尚造成 CD95蛋白質的活化，此二原因均為誘發PMN細胞活化相關caspase路徑導致PMN細胞凋亡的原因。因此，本研究可以獲得以下結論：連續性高強度運動後所誘發PBMC的apoptosis可能是因氧化壓力藉由粒線體活化途徑進行；而PMN則是由粒線體活化途徑與Fas / FasL活化途徑同時誘導apoptosis的發生。

The intensity and duration of exercise will strongly influence the physical responses. After high intensity exercise (85% VO2max), the reactive oxygen species (ROS) are numerously generated, which makes an imbalance between the oxidatants and antioxidatants of organism to result in oxidative stress. Oxidative stress can potentially induce immune cell programmed cell death, or called apoptosis after high intensity exercise. However, the possible mechanisms have not been investigated. The purpose of this study was to investigate the effect of consecutive high intensity exercise induced-oxidative stress on leukocytes apoptosis. Twelve volunteers (22.8 ± 2.39 yrs) were recruited into this study. All subjects performed the session of aerobic exercise at an intensity of 85% VO2max for 30 min daily for 3 consecutive days. 20 mL of venous blood samples were collected before first day (D1) of exercise, immediately postexercise on the first day (D1’), preexercise on the third day (D3), immediately postexercise on the third day, the fifth day (D5) and the seventh day (D7). The oxidative stress and apoptosis in leukocytes were measured by flow cytometry, and the transcription and translation of the apoptosis associated genes also were determined by RT-PCR and western blotting. The results showed that exercise at 85% VO2max intensity leaded to a depletion of intracellular glutathione (GSH) (p＜.001) and quite often accompanied by a concomitant increase in ROS (p＜.001). This phenomenon could contribute to oxidative stress and apoptosis. In PBMC, it is extremely critical steps that both the loss of the mitochondrial transmembrane potential (MTP) (p＜.001) and the release of cytochrome c from the inner membrane of mitochondria can potentially trigger caspase cascade activation, then results in apoptosis. As for PMN, not only collapse of MTP and cytochrome c released to cytosol from mitochondria but also CD95 receptor activated particularly (p＜.001) could produced caspase cascade. In conclusion, it is proposed that the consecutive high intensity exercise will increase oxidative stress and induce PBMC apoptosis via mitochondria apoptotic pathway, whereas consecutive high intensity exercise induced PMN apoptosis were mediated via both mitochondria and Fas / FasL activated pathways.

目錄
中文摘要…………………………………………………………… I
英文摘要…………………………………………………………… III
謝誌 ………………………………………………………………… V
目錄………………………………………………………………… VII
圖目錄……………………………………………………………… IX
表目錄……………………………………………………………… X
附錄 ………………………………………………………………… XI
第壹章 緒論 …………………………………………………………1
第一節 前言 ………………………………………………… 1
第二節 問題背景……………………………………………… 2
第三節 研究的重要性………………………………………… 4
第四節 研究目的……………………………………………… 4
第五節 研究策略……………………………………………… 5
第六節 研究範圍與限制……………………………………… 5
第七節 名詞操作性定義……………………………………… 6
第貳章 相關文獻探討……………………………………………… 10
第一節 氧化壓力的定義……………………………………… 10
第二節 運動中活性氧的來源………………………………… 10
第三節 細胞計劃性凋亡的功能與特徵……………………… 14
第四節 運動與細胞凋亡……………………………………… 23
第參章 研究方法與步驟 ……………………………………………26
第一節 受試者 …………………………………………………26
第二節 實驗設計與實驗變項 …………………………………26
第三節 最大氧攝取量的測量與運動訓練 ……………………27
第四節 實驗材料與方法 ………………………………………28
第五節 實驗控制 ………………………………………………37
第六節 統計方法 ………………………………………………38
第肆章 結果 ……………………………………………………… 39
第一節 受試者基本資料……………………………………… 39
第二節 累積性高強度運動誘發氧化壓力對週邊血液單核球細胞凋亡的影響 ……………………………………… 39
第三節 累積性高強度運動誘發氧化壓力對多形核白血球細胞凋亡的影響 ……………………………………… 50
第伍章 討論 ……………………………………………………… 61
第一節 累積性高強度運動誘發氧化壓力對週邊血液單核球細胞凋亡的影響 ……………………………………… 61
第二節 累積性高強度運動誘發氧化壓力對多形核白血球細胞凋亡的影響 ……………………………………… 70
第三節 累積性高強度對不同白血球亞型細胞凋亡的影響… 76
第陸章 結論與建議 ……………………………………………… 79
第一節 結論 ………………………………………………… 79
第二節 建議 ………………………………………………… 79
第三節 未來展望 …………………………………………… 80
參考文獻 ………………………………………………………………82
一、 中文部分………………………………………………… 82
二、 英文部分………………………………………………… 82
附錄 ……………………………………………………………………96

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