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題名:運動訓練對氧化態低密度脂蛋白抑制流體媒介之血管舒張作用的生理影響
作者:林嘉志
作者(外文):Lin, Chia-Chih
校院名稱:國立臺灣師範大學
系所名稱:體育研究所
指導教授:謝伸裕
陳君侃
學位類別:博士
出版日期:1999
主題關鍵詞:內皮細胞型一氧化氮合成運動訓練氧化態低密度脂蛋白eNOS: endothelial nitric oxide synthaseexercise trainingOx-LDL: oxidized low-density lipoprotein
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運動訓練對氧化態低密度脂蛋白抑制
流體媒介之血管舒張作用的生理影響
摘要
前人的研究指出長期運動訓練可以促進內皮細胞型一氧化氮合成 (endothelial nitric oxide synthase, eNOS) 的基因表現,而流體誘發的血管舒張作用也被證明主要是透過eNOS基因表現的增加及活化。此外,氧化態低密度脂蛋白 (oxidized low density lipoprotein, Ox-LDL) 對eNOS基因表現有減少調節作用。為比較Ox-LDL對長期運動大鼠的流體誘發的動脈血管舒張能力的影響,本實驗特別設計了一套半活體灌流的裝置。週齡5週的大鼠施以分組後,運動組以原地跑步機進行每天60 min,每週5天,持續15-20週中等強度 (約70 % VO2peak) 的跑步運動訓練後,移除股動脈後施以不同流速 (0-15 ml/hr)、固定壓力 (60 mmHg) 的灌流程序。另外Ox-LDL對主動脈上eNOS蛋白質及mRNA的影響也分別以西方轉漬法 (Western blot) 及反轉錄聚合鏈鎖反應 (reverse transcriptional polymerase chain reaction, RT-PCR) 來分析。
結果發現:(1) Ox-LDL均會降低兩組大鼠流體誘發的動脈血管舒張能力;但是運動組在無論有無處理Ox-LDL條件之下,仍較控制組有較好的血管舒張能力;(2)運動組主動脈有較多的eNOS蛋白質及mRNA表現,雖然受Ox-LDL作用後,其eNOS蛋白質及mRNA的減少程度明顯高於控制組,但其eNOS蛋白質仍稍微多於未受Ox-LDL作用的控制組;(3) HDL可保護Ox-LDL對eNOS蛋白質的減少作用;(4) EGTA無法反轉Ox-LDL 對eNOS的抑制作用,表示抑制機制可能不是透過Ca+2活化的蛋白分解而引起;(5) 分離自運動組的LDL顯示較不易受到Cu+2在活體外 (in vitro) 所進行氧化作用的影響。
本實驗的結論為:長期運動訓練的大鼠較不易受到Ox-LDL造成的一些促粥狀動脈硬化 (proatherogenic) 效應的影響。然而,由於運動組eNOS蛋白質及mRNA表現明顯受到Ox-LDL的作用而減少,顯示在Ox-LDL存在條件下,愈多NO可能伴隨更多的危險。這個發現可能可以解釋少數優秀運動員,特別是優秀馬拉松選手,亦無法避免因粥狀動脈硬化性疾病導致的猝死案例。
關鍵詞:
內皮細胞型一氧化氮合成 (endothelial nitric oxide synthase, eNOS)
運動訓練 (exercise training)
氧化態低密度脂蛋白 (oxidized low-density lipoprotein, Ox-LDL)
Oxidized LDL and Flow-mediated Vasodilation
:Effect of Chronic Exercise Training
Abstract
Chronic exercise training has been shown to induce aortic endothelial nitric oxide synthase (eNOS) mRNA expression and activation resulting in a greater flow-induced vasodilation. On the other hand, oxidized low-density lipoprotein (Ox-LDL) has been shown to inhibit vasodilation by downregulating eNOS mRNA expression. To compare the effect of Ox-LDL on the flow-induced arterial vasodilatability in chronic exercise-trained and untrained rats, a semi in vivo perfusion system was designed. Five-week-old male Wistar rats were divided into exercise and control groups. After fifteen to twenty weeks of treadmill training at moderate intensity (approximately 70 % VO2peak) for 60 min per day, five days per week, femoral arteries were removed and perfused at varying flow rates under a constant pressure of 60 mmHg. The effects of Ox-LDL on aortic eNOS protein and mRNA expression were also examined by Western blot and reverse transcriptional polymerase chain reaction (RT-PCR).
The results showed that: (1) Ox-LDL reduced the flow-induced vasodilation in both groups; however, vessels from the exercise-primed rats exhibited better vasodilatability with and without Ox-LDL treatment; (2) eNOS protein and mRNA levels were elevated in the aortae of the exercise-primed rats. Exposure to Ox-LDL caused a prominent reduction of both eNOS mRNA and protein in the exercise-primed rats; however, the overall eNOS protein level in the aortae of the Ox-LDL treated exercise-primed rats was still slightly higher than that of the aortae of the control rats; (3) Cotreatment with HDL prevented Ox-LDL-induced aortic eNOS protein reduction in both groups; (4) EGTA treatment could not reverse the inhibitory effect, indicating that the mechanism may not by mediated by Ca+2-activated proteases; (5) LDL isolated from exercise-primed rats exhibited a higher resistance to Cu+2 induced oxidation in vitro.
In conclusion, the present study shows that chronic exercise-primed rats are less susceptible to some of the proatherogenic effects of Ox-LDL. However, in the exercise group, the eNOS protein and mRNA expression are more profundly inhibited by Ox-LDL, indicating that more risk will be accompanied by more NO if Ox-LDL is present. This finding may explain why atherosclerotic cardiac disease could develop in elite athletes, especially marathon runners, and has been a major cause of sudden death in athletes.
Key words:
eNOS: endothelial nitric oxide synthase
exercise training
Ox-LDL:oxidized low-density lipoprotein
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