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系統識別號 U0026-0812200915050578
論文名稱(中文) 急性運動對於高血壓鼠由胰島素與類胰島素生長因子-1調節之血管功能的影響
論文名稱(英文) Effects of Acute Exercise on Insulin-mediated and Insulin-like Growth Factor-1-mediated Vascular Function in Spontaneously Hypertensive Rats
校院名稱 成功大學
系所名稱(中) 物理治療研究所
系所名稱(英) Department of Physical Therapy
學年度 97
學期 1
出版年 98
研究生(中文) 葉謙魁
研究生(英文) Chien-Kuei Yeh
電子信箱 jka126@gmail.com
學號 t6695404
學位類別 碩士
語文別 中文
論文頁數 63頁
口試委員 指導教授-楊艾倫
口試委員-林尊湄
口試委員-李信達
中文關鍵字 胰島素  類胰島素生長因子-1  血管舒張反應  高血壓  運動 
英文關鍵字 insulin  insulin-like growth factor-1  exercise  vasorelaxation  hypertension 
學科別分類
中文摘要 背景和目的:近年研究顯示,胰島素(insulin)和類胰島素生長因子-1(insulin-like growth factor-1, IGF-1)是保護和調節心血管功能的兩種重要荷爾蒙,它們藉由刺激血管內皮細胞產生一氧化氮(nitric oxide, NO),擴散到平滑肌細胞引起血管舒張反應,兩種荷爾蒙的訊息傳遞路徑是它們接受器結合之後,會與insulin receptor substrate (IRS)組成複合體(complex),活化phosphatidylinositol 3-kinase (PI3-K),進一步活化一氧化氮合成(NO synthase, NOS),產生一氧化氮。目前的證據顯示高血壓情形下,乙醯膽鹼(acetylcholine, ACh)調節之血管舒張反應是明顯受損的,而藉由運動可以改善此受損之血管舒張反應,但關於胰島素和類胰島素生長因子-1調節血管功能的研究仍不足,也沒有研究是探討急性運動對於高血壓在胰島素和類胰島素生長因子-1調節之血管舒張反應的效用,所以本研究採用高血壓疾病的動物模式,探討急性運動對於胰島素和類胰島素生長因子-1調節的血管功能之影響,並且了解背後之潛在機制。

方法:將自發性高血壓大鼠(spontaneously hypertensive rats, SHR)隨機分成運動組和非運動組,再以週齡相符的正常血壓大鼠(Wistar Kyoto rats, WKY rats)作為對照組。運動組以跑步機給予單次中度運動介入,運動時間為60分鐘。運動結束後,立即取下大鼠之胸主動脈,作為後續測量血管舒張反應之用。

主要結果為:(1)相較於正常血壓大鼠,自發性高血壓大鼠由胰島素與類胰島素生長因子-1所調節的血管舒張反應是明顯減少的;(2)急性中度運動介入後,會明顯地增加自發性高血壓大鼠由胰島素與類胰島素生長因子-1所調節的血管舒張反應;(3)運動介入所造成的改變主要與PI3-K和一氧化氮合成有關;(4)自發性高血壓大鼠由胰島素與類胰島素生長因子-1所調節的血管舒張反應明顯減少和超氧陰離子的增加有關。

結論:高血壓會造成胰島素和類胰島素生長因子-1所調節的血管舒張反應變差,這樣的改變和高血壓造成的氧化性壓力增加有關,而經過急性中度運動介入後,胰島素和類胰島素生長因子-1所調節的血管舒張反應有明顯改善的現象。本研究提供運動如何改善高血壓之血管病變之部份理論基礎。
英文摘要 Background and purpose: Recent studies have indicated that insulin and insulin-like growth factor-1 (IGF-1) are important hormones that protect and regulate cardiovascular function. These two hormones can produce nitric oxide (NO) from endothelial cells, which diffuses to smooth muscle cells and induces vasorelaxation. Insulin and IGF-1 cause phosphorylation of phosphatidylinositol-3 kinase (PI3-K), activate nitric oxide synthase (NOS), and lead to NO production. Furthermore, several studies have reported that the acetylcholine (ACh)-mediated vasorelaxation is impaired in hypertension. Also, exercise has been found to improve this adverse effect. However, the effects of acute exercise on insulin-mediated and IGF-1-mediated vasorelaxation in hypertension remain unclear. Therefore, the purpose of this study was to examine the effects of acute exercise on insulin-mediated and IGF-1-mediated vascular function, as well as its underlying mechanisms, in spontaneously hypertensive rats (SHR).

Methods: SHR were randomly divided into acute exercise (SHR+Ex) and sedentary groups. Age-matched Wistar-Kyoto (WKY) rats were used as control group. Single exercise intervention was conducted in the acute exercise group by running on a treadmill for sixty minutes. Immediately after exercise, the thoracic aortas of rats were isolated for the measurement of vasorelaxation.

Results: We found that, (1) compared with WKY, the insulin-mediated and IGF-1-mediated vasorelaxation were significantly decreased in the SHR group; (2) acute moderate exercise significantly improved insulin-mediated and IGF-1-mediated vasorelaxation in the SHR+Ex group; (3) the alternations on insulin-mediated and IGF-1-mediated vasorelaxation were mainly caused by release of PI3-K and NOS; (4) the impairments of insulin-mediated and IGF-1-mediated vasorelaxation in SHR were associated with the increase of oxidative stress.

Conclusion: Our results suggested that insulin-mediated and IGF-1-mediated vasorelaxation were impaired in hypertension, which was associated with the increase of oxidative stress. Acute moderate exercise would improve the vasorelaxation induced by insulin and IGF-1; This study provides parts of the underlying theoretical base for the improvements of hypertension-induced vascular impairment through exercise intervention.
論文目次 緒論---------------------------------------------------------------------------------- 1
材料與方法------------------------------------------------------------------------- 12
實驗動物----------------------------------------------------------------------- 12
急性中度運動----------------------------------------------------------------- 12
休息時心搏率和血壓的量測----------------------------------------------- 13
動物犧牲及血管的製備----------------------------------------------------- 13
血管舒張反應的測量------------------------------------------------------ 15
免疫組織染色---------------------------------------------------------------- 18
統計分析--------------------------------------------------------------------- 19
結果-------------------------------------------------------------------------------- 20
實驗大鼠之基本生理參數------------------------------------------------ 20
累積劑量乙醯膽鹼所調節之血管舒張反應變化--------------------- 20
累積劑量胰島素和類胰島素生長因子-1所調節之血管舒張反應變化------- 21
加入抑制劑Wortmannin及L-NAME後血管舒張反應之變化----- 22
加入SOD後血管舒張反應之變化-------------------------------------- 24
累積劑量SNP所調節之血管舒張反應變化-------------------------- 24
一氧化氮合成之蛋白質分佈情形和表現量變化----------------- 25
討論-------------------------------------------------------------------------------- 26
表----------------------------------------------------------------------------------- 37
圖----------------------------------------------------------------------------------- 38
參考文獻-------------------------------------------------------------------------- 52
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