臺灣博碩士論文加值系統

背景與目的：運動會影響 CD4+ 淋巴球的活性，進一步影響免疫功能，取決於運動的形式、強度以及時間。本篇研究探討結合有氧與阻力型的交替式運動訓練對於 CD4+ 淋巴球凋亡與自噬作用的影響。
方法：本研究收取 36 位健康男性，在運動訓練前後分別進行最大運動測試 (maximal exercise test) 、大腿肌群之疲勞測試 (fatigue test) 以及最大自主收縮測試 (maximal voluntary contraction test) 。所有受試者皆隨機分派至連續式運動訓練組 (continuous exercise training group, CT) 或間隔式運動訓練組 (alternative exercise training group, AT)。連續式運動訓練組：以 60% 最大攝氧量 (VO2max) 進行 30 分鐘腳踏車有氧運動訓練，以角速度 120°/s 進行 6~10 回膝關節活動之阻力型訓練。間隔式訓練組：以 40% 及 80% 最大攝氧量 (VO2max) 進行 30 分鐘腳踏車有氧運動訓練，以角速度 60°/s 與 180°/s 進行 6~10 回膝關節活動之阻力型訓練。訓練頻率為一週 3 天腳踏車訓練以及 2 天的阻力型訓練，為期六週。於最大運動測試前後抽血以各項生物標記觀察 CD4+ 淋巴球凋亡 (apoptosis) 與自噬作用 (autophagy) 之表現，並以腎上腺素刺激及加入各項自由基阻斷劑模擬運動時面臨壓力荷爾蒙與氧化壓力的情形觀察各項機制。
結果：急性劇烈運動會刺激 CD4+ 淋巴球腎上腺素信號傳遞，粒線體膜電位下降，凋亡蛋白3 (caspase-3) 活性上升以及向上調控 lysosomal-associated membrane protein 2 (LAMP-2) ，過程中伴隨 phosphatidylserine (PS) 外翻及 acridin orange (AO) 染劑表現量的上升。經過 6 週的運動訓練後，在交替式訓練組會降低劇烈運動時 CD4+ 淋巴球對腎上腺素的敏感度 (1-AR、PKA、GRK2表現量下降)、降低凋亡的情形，表現在粒線體膜電位、caspase-3、PS外翻的表現上，然而對於自噬作用則無顯著差異。腎上腺素刺激會誘發劇烈運動時 CD4+ 淋巴球的凋亡的現象，可能來自於NADPH oxidase路徑產生自由基帶來的影響。
結論：本篇研究提供一個新的運動介入模式，相較於連續式運動，透過交替式運動模式可以提升周邊與中樞的運動表現量，增進CD4+淋巴球對抗壓力荷爾蒙與氧化壓力進而減緩細胞凋亡的情形。

Background and Purpose: Physical exercise may influence CD4+ lymphocyte activity and potentially modulate adaptive immune function, it dependents on the type, intensity and duration of exercise. This study investigated how combined aerobic and resistance alternative exercise training influenced apoptosis and autophagy of CD4+ lymphocytes.
Methods: 36 sedentary healthy men performed a maximal exercise test (by bicycle ergometer), muscle fatigue test and maximal voluntary contraction test (by isokinetic dynamometer) before and after exercise training, respectively. All subjects were randomly divided into continuous exercise training group (CT) or alternative exercise training group (AT). CT group: aerobic training (60%VO2max, 30 mins) combined with knee flexion/extension resistance training (isokinetic contraction with 120°/s for 6 to 10 sessions); AT group: aerobic training (3-minute intervals at 40% and 80% of VO2max, 30 mins) combined with knee flexion/extension resistance training (isokinetic contraction with 60°/s, 180°/s for 6 to 10 sessions). The training frequency of endurance exercise training is 3 days/week, and resistance exercise is 2 days/week for 6 weeks. Apoptotic and autophagic responses in CD4+ lymphocyte were determined by monitoring corresponding biological markers in resting and immediately after maximal exercise test. CD4+ lymphocyte is stimulated by epinephrine and inhibitors to investigate the pathway of exercise induced stress hormone and oxidative stress makes the impact on apoptosis and autophagy.

Result: The experimental results demonstrated that strenuous, acute exercise simultaneously enhance -adrenergic signaling, lost mitochondrial membrane potential (MTP), activated caspase-3, and up-regulated LAMP-2, which were accompanied by the increases of phosphatidyl serine (PS) exposure, and staining of acridin orange (AO) in CD4+ lymphocytes. After 6 weeks alternative exercise training decreased CD4+ lymphocyte -adrenergic signaling (by lower -AR, PKA, GRK2) and apoptosis responses of MTP, caspase-3 and PS exposure. However, there is no significant effect on autophagic response. The apoptotic response stimulated by epinephrine might from the NADPH oxidase pathway releasing free radical.
Conclusion: This research device a new type of exercise intervention. Compare to CT, AT is better in central and peripheral physical performances, and enhances CD4+ lymphocyte anti-stress hormone and anti- oxidative stress capacity to reduce the apoptosis response when in the strenuous exercise.

指導教授推薦書
口試委員會審定書
國家圖書館授權書..........................................iv
長庚大學著作授權書.........................................v
誌謝....................................................vi
中文摘要.................................................viii
英文摘要.................................................x
目錄....................................................xii
圖表目錄.................................................xvii
第一章 緒論 (Introduction).............................- 1 -
第一節 研究背景及目的......................................- 1 -
第二節 研究假設...........................................- 2 -
第二章 文獻回顧 (Literature Review).....................- 3 -
第一節 CD4+淋巴球.........................................- 3 -
第二節 運動與免疫功能......................................- 4 -
A. 運動 J 型曲線....................................- 4 -
B. 運動與淋巴球數目的變化.............................- 4 -
C. 運動與壓力荷爾蒙..................................- 5 -
D. 運動與氧化壓力....................................- 7 -
第三節 細胞死亡機制........................................- 9 -
A. 細胞凋亡機制......................................- 9 -
B. 自噬作用機制......................................- 10 -
第四節 運動處方的制定.......................................- 12 -
A. 有氧間隔式運動....................................- 12 -
B. 阻力型運動........................................- 12 -
C. 等速肌力運動......................................- 13 -
D. 阻力型運動結合有氧運動..............................- 14 -
E. 交替式運動........................................- 15 -
第三章 實驗設計 (Experimental Design)......................- 16 -
第一節 實驗材料 (Materials)................................- 16 -
A. 試劑 (Reagents)..................................- 16 -
B. 抗體 (Antibody)..................................- 16 -
C. 儀器 (Instruments)...............................- 17 -
第二節 實驗方法 (Methods)..................................- 19 -
A. 研究對象..........................................- 19 -
B. 實驗流程..........................................- 19 -
C. 運動測試..........................................- 20 -
D. 受試者分組與運動訓練處方.............................- 23 -
E. 淋巴球純化分離 (Lymphocyte Isolation)..............- 24 -
F. CD4+淋巴球刺激條件.................................- 25 -
G. CD4+ 淋巴球染色...................................- 25 -
H. CD4+ 與 CD8+ 淋巴球比例之觀察.......................- 25 -
I. 觀察 CD4+ 淋巴球腎上腺信號傳遞標記....................- 26 -
J. 觀察 CD4+ 淋巴球自體吞噬標記.........................- 26 -
K. 觀察 CD4+ 淋巴球凋亡標記............................- 27 -
L. 觀察自由基對CD4+淋巴球凋亡和自噬的影響途徑..............- 28 -
第三節 統計方法 (Statistical analysis).....................- 30 -
第四章 結果 (Results)...................................- 31 -
第一節 受試者基本資料、身體狀況和活動情形調查....................- 31 -
第二節 兩組於訓練前後之心肺適能表現............................- 32 -
第三節 兩組於訓練前後之肌力、肌耐力表現 .........................- 33 -
第四節 淋巴球數目及比例變化情形................................- 33 -
第五節 兩組運動訓練對 CD4+ 淋巴球在最大運時腎上腺素信號傳遞路徑的影響...... - 34 -
第六節 兩組運動訓練對 CD4+ 淋巴球自噬作用及凋亡的影響.............- 34 -
第七節 經腎上腺素刺激 CD4+ 淋巴球自噬及凋亡作用的影響.............- 35 -
第八節 運動誘發腎上腺素刺激所產生的自由基對 CD4+ 淋巴球凋亡及自噬作用的影響..- 35 -
第五章 討論 (Discussions)................................- 36 -
第一節 兩組訓練對於最大運動表現的影響...........................- 36 -
第二節 兩組訓練對於淋巴球數目和比例變化情形......................- 38 -
第三節 兩組訓練對於CD4+淋巴球腎上腺信號傳遞的影響................- 39 -
第四節 兩組訓練對於CD4+淋巴球自噬與凋亡作用的影響.................- 41 -
第五節 兩組訓練對腎上腺素誘發自由基對 CD4+ 淋巴球凋亡與自噬作用的影響....- 45 -
第六節 研究限制.............................................- 47 -
第六章 結論 (Conclusion).................................- 48 -
圖表附錄...................................................- 49 -
參考文獻 (References).......................................-72-
附錄........................................................-84-

圖表目錄
表一 人體基本測量數值與最大運動表現.........................- 49 -
表二 腿部伸肌肌力測試運動表現..............................- 50 -
圖一 淋巴球數目.........................................- 51 -
圖三 CD4、CD8 淋巴球絕對數量.............................- 53 -
圖二 CD4/CD8 淋巴球相對比例..............................- 52 -
圖四 CD4+淋巴球B1-Adrenergic Receptor (B1-AR) 表現量......-54-
圖五 CD4+淋巴球PKA Phosphorylation (p-PKA+) 表現量........-55-
圖六 CD4+淋巴球G protein-coupled Receptor Kinase2(GRK2)表現量........-56-
圖七 CD4+淋巴球 Mammalian Target of Rapamycin (mTOR)表現量...........-57-
圖八 CD4+淋巴球 LAMP2 表現量..............................-58-
圖九 CD4+淋巴球 AO (arcridine orange) 表現量..............-59-
圖十 CD4+淋巴球粒線體膜電位 (MTP) 改變量.....................-60-
圖十一 CD4+淋巴球凋亡酶3 (caspase-3) 表現量.....................-61-
圖十二 CD4+淋巴球 PS 外翻情形...................................-62-
圖十三 腎上腺素刺激 CD4+淋巴球 Autophagy 相關蛋白表現..............-63-
圖十四 腎上腺素刺激 CD4+淋巴球 Apoptosis 相關蛋白表現..............-64-
圖十五 腎上腺素刺激 CD4+淋巴球產生自由基對PS外翻的影響...............-65-
圖十六 腎上腺素刺激 CD4+ 淋巴球產生自由基對 caspase-3 活化情形的影響..-66-
圖十七 腎上腺素刺激 CD4+淋巴球產生自由基對 LAMP2 的影響 ............-67-
圖十八CD4、CD8淋巴球流式細胞儀分析圖..............................-68-
圖十九CD4+淋巴球腎上腺信號傳遞相關蛋白流式細胞儀分析圖................-69-
圖二十CD4+淋巴球自噬作用相關蛋白流式細胞儀分析圖.....................-70-
圖二十一CD4+淋巴球凋亡作用相關蛋白流式細胞儀分析圖....................-71-

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85. 陳婉翎，<低氧運動訓練對淋巴球之凋亡與再分佈的影響>，長庚大學，碩士論文，民國98年
86. 陳怡靜，<有氧間隔性運動訓練及中度持續性運動訓練對發炎性血栓的影響>，長庚大學，碩士論文，民國100年