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研究生:吳思頷
研究生(外文):Wu , Sih-Han
論文名稱:運動和原兒茶酸對於高血壓之心血管功能的影響
論文名稱(外文):Effects Of Exercise And Protocatechuic Acid On Cardiovascular Function In Hypertension
指導教授:楊艾倫 
指導教授(外文):Yang , Ai-Lun
口試委員:黃滄海
口試日期:2012-06-28
學位類別:碩士
校院名稱:臺北巿立體育學院
系所名稱:運動科學研究所
學門:民生學門
學類:運動科技學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:117
中文關鍵詞:原兒茶酸、運動、高血壓、心血管功能、抗氧化能力
外文關鍵詞:protocatechuic acid, exercise, hypertension, cardiovascular function, antioxidant
相關次數:
  • 被引用被引用:1
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  • 下載下載:80
  • 收藏至我的研究室書目清單書目收藏:3
背景和目的:由國民健康局的資料顯示近年來國人的十大死因趨向於以心臟血管等疾病為主,而高血壓為其主要的危險因子之一。高血壓的情形下,血管內皮功能會有受損的情形。此外,氧化壓力上升對於血管功能失調和高血壓的發病機制,扮演一個重要的角色。原兒茶酸 (protocatechuic acid, PCA) 屬多酚類化合物,且為天然的抗氧化物,先前研究指出原兒茶酸具有很強的抗氧化能力。目前已知運動訓練可以有效改善心血管功能,然而尚無研究去探討和比較原兒茶酸和運動訓練對於高血壓心血管功能的影響,因此本研究目的是探討和比較長期原兒茶酸和運動介入對於高血壓心血管功能的影響,並探究其生理調控機制。方法:本研究以動物實驗模式進行,將六周大之高血壓大鼠隨機分成高血壓組 (不做任何介入) (spontaneously hypertensive rat, SHR)、高血壓餵食原兒茶酸組 (SHR+PCA) 和高血壓運動訓練組 (SHR+EX),並以周齡相符之正常血壓之大鼠 (Wistar-Kyoto rat, WKY) 作為對照組,實驗共分為四組。高血壓餵食原兒茶酸組為每天每公斤體重給予200毫克的原兒茶酸添加於飲用水中,餵食八週;而高血壓運動訓練組則是每天規律進行跑步機運動訓練六十分鐘,每週五天,為期八週。於八週介入期間和結束後,分別測量四組血壓、心跳、和血管舒張功能等參數,並檢測血液抗氧化酵素的活性與脂質氧化傷害的程度,最後亦分析血管內皮功能相關蛋白質的表現量。結果:本研究發現於八週原兒茶酸和運動介入後,與不作任何介入之高血壓組相較下,結果顯示:(1) 顯著降低血壓 (2) 增加由乙醯膽鹼、胰島素和類胰島素生長因子-1 所調節之血管舒張功能 (3) 降低胰島素阻抗 (4) 增加一氧化氮生成量 (5) 增加血管中一氧化氮合成酶、胰島素受器和類胰島素生長因子-1 受器蛋白質表現量 (6) 增加抗氧化能力。結論:本研究顯示原兒茶酸和運動介入皆可有效改善部分之高血壓心血管功能,建議未來可作為高血壓族群之臨床介入方式。
Background and purpose:Oxidative stress elevation plays an important role in the pathogenesis of endothelial dysfunction and hypertension. Previous studies have indicated that the Protocatechuic acid (PCA) has strong antioxidant capacity. Moreover, exercise has been known to improve cardiovascular function. However, few research explored and compared the effects of PCA and exercise intervention on cardiovascular function in hypertension. Thus, the purpose of this study was to investigate the effects of long-term PCA and exercise intervention on cardiovascular function in hypertension, and explore its physiological mechanisms. Methods:Six-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. The SHR were randomly divided into sedentary control (SHR), SHR with PCA feeding (SHR+PCA), and SHR with exercise training (SHR+EX) groups. The SHR+PCA group was feeded with, the PCA solution (0.2 g/kg body weight per day), adjusted from the daily water consumption, for a total of 8 weeks. In addition, the SHR+EX group was trained by the treadmill at moderate intensity for 5 days/week, 8 weeks. At the end of experiments, the cardiovascular responses were measured and compared among four groups. The serum levels of antioxidants and oxidants were examined, and the related vascular protein expression was also evaluated. Results:We found that, compared with the sedentary control SHR, the PCA and exercise intervention significantly could:(1) lower blood pressure; (2) increase acetylcholine-, insulin-, and IGF-1-induced vasodilation responses in aortas; (3) reduce insulin resistance; (4) increase nitric oxide production; (5) increase the protein expression of aortic eNOS, IR, and IGF-1R (6) increase the antioxidant activities. Conclusion:Either PCA or exercise training could significantly improve parts of cardiovascular function in hypertension, which may be applied in hypertensive population clinically.


中文摘要………………………………………………………………iv
英文摘要………………………………………………………………vi
謝誌……………………………………………………………………viii
目錄……………………………………………………………………ix
表目錄…………………………………………………………………xiv
圖目錄…………………………………………………………………xv

第壹章 緒論………………………………………………………………1
第一節 研究背景……………………………………………………1
第二節 研究目的……………………………………………………2
第三節 研究問題……………………………………………………2
第四節 研究假設……………………………………………………3
第貳章 文獻探討…………………………………………………………4
第一節 高血壓………………………………………………………4
第二節 自由基與體內抗氧化防禦系統……………………………6
一、 自由基……………………………………………………6
二、 體內抗氧化防禦系統………………………………………9
第三節 高血壓與氧化壓力………………………………………11
第四節 多酚與高血壓……………………………………………12
第五節 原兒茶酸 (protocatechuic acid, PCA)……………………14
第六節 胰島素與類胰島素生長因子……………………………16
第七節 運動與高血壓……………………………………………18
第参章 材料與方法……………………………………………………20
第一節 實驗動物來源與飼養……………………………………20
第二節 長期運動訓練計畫………………………………………21
第三節 休息時心搏率與血壓測量之方法………………………22
第四節 胰島素阻抗指標………………………………………23
一、 血糖偵測…………………………………………………23
二、 胰島素含量………………………………………………23
三、 Homeostasis model assessment for insulin resistance (HOMA-IR) ……………………………………………23
第五節 血管舒張反應之量測……………………………………24
一、 血清的製備………………………………………………24
二、 血管段的製備……………………………………………24
三、 血管段活性測試…………………………………………25
四、 內皮依賴性血管舒張反應………………………………26
五、 非內皮依賴性血管舒張反應……………………………26
六、 一氧化氮合成酶和 PI3-kinase 的作用…………………26
第六節 一氧化氮含量分析………………………………………27
第七節 檸檬酸合成酶之活性分析………………………………28
第八節 西方墨點法………………………………………………29
一、 組織樣本前處理…………………………………………29
二、 蛋白質定量………………………………………………29
三、 蛋白質變性………………………………………………30
四、 SDS-PAGE 配置…………………………………………30
五、 跑電泳膠片………………………………………………31
六、 電泳膠片的轉漬 (membrane transfer) 及 blotting………31
七、 接上一級抗體與二級抗體………………………………31
第九節 脂質過氧化分析和抗氧化酵素之活性分析……………32
一、 脂質過氧化丙二醛含量分析……………………………32
二、 過氧化氫酶之活性分析…………………………………33
第十節 統計分析………………………………………………34
第肆章 結果……………………………………………………………35
第一節 基本生理參數……………………………………………35
第二節 胰島素阻抗指標…………………………………………36
第三節 血管舒張反應之量測……………………………………36
一、 乙醯膽鹼所調節之血管舒張反應………………………36
二、 胰島素所調節之血管舒張反應…………………………37
三、 類胰島素生長因子所調節之血管舒張反應……………38
四、 SNP所調節之血管舒張反應……………………………38
五、 L-NAME和 Wortmannin 抑制劑對於乙醯膽鹼所調節之血管舒張反應………………………………………………39
六、 L-NAME和Wortmannin 抑制劑對於胰島素所調節之血管舒張反應……………………………………………………40
七、 L-NAME和Wortmannin 抑制劑對於類胰島素生長因子所調節之血管舒張反應……………………………………40
第四節 一氧化氮含量分析………………………………………41
第五節 檸檬酸合成酶之活性……………………………………42
第六節 血管功能相關之蛋白質表現量…………………………42
一、 內皮細胞一氧化氮合成酶之蛋白質表現量 ……………42
二、 胰島素受器之蛋白質表現量…………………………43
三、 類胰島素生長因子之蛋白質表現量…………………43
第七節 脂質過氧化物含量分析和抗氧化酵素之活性分析……43
一、 脂質過氧化丙二醛含量分析……………………………43
二、 抗氧化酵素之活性分析…………………………………44
第伍章 討論與結論…………………………………………………45
參考文獻…………………………………………………………………58
















表目錄

表1、八週原兒茶酸和運動介入後之體重、休息時心跳和血壓參數…82
表2、八週原兒茶酸和運動介入後之空腹血糖值、胰島素含量和 Homeostasis model assessment for insulin resistance (HOMA-IR) ………………………………………………………83
表3、八週原兒茶酸和運動介入後之比目魚肌檸檬酸合成酶活性……84












圖目錄

圖1、經八週原兒茶酸和運動介入後,累積劑量之乙醯膽鹼對於大鼠胸主動脈血管所調節血管舒張反應曲圖…………………………85
圖2、經八週原兒茶酸和運動介入後,累積劑量之胰島素對於大鼠胸主動脈血管所調節血管舒張反應曲線圖…………………………86
圖3、經八週原兒茶酸和運動介入後,累積劑量之類胰島素生長因子-1對於大鼠胸主動脈血管所調節血管舒張反應曲線圖…………87
圖4、經八週原兒茶酸和運動介入後,累積劑量之劑量 SNP 對於大鼠胸主動脈血管所調節血管舒張反應曲線圖……………………88
圖5、經八週原兒茶酸和運動介入後,在L-NAME (10-6M)抑制劑作用下,乙醯膽鹼對於大鼠胸主動脈血管所調節之血管舒張反應結果…………………………………………………………………89
圖6、經八週原兒茶酸和運動介入後,在wortmannin (3×10-7M) 抑制劑作用下,乙醯膽鹼對於大鼠胸主動脈血管所調節之血管舒張反應結果………………………………………………………………90
圖7、經八週原兒茶酸和運動介入後,在L-NAME (10-6M)抑制劑作用下,胰島素對於大鼠胸主動脈血管所調節之血管舒張反應結果…………………………………………………………………91
圖8、經八週原兒茶酸和運動介入後,在wortmannin (3×10-7M) 抑制劑作用下,胰島素對於大鼠胸主動脈血管所調節之血管舒張反應結果…………………………………………………………………92
圖9、經八週原兒茶酸和運動介入後,在L-NAME (10-6M)抑制劑作用下,類胰島素生長因子-1對於大鼠胸主動脈血管所調節之血管舒張反應結果………………………………………………………93
圖10、經八週原兒茶酸和運動介入後,在wortmannin (3×10-7M) 抑制劑作用下,類胰島素生長因子-1對於大鼠胸主動脈血管所調節之血管舒張反應結果……………………………………………94
圖11、 八週原兒茶酸和運動介入後之一氧化氮 (Nitrate+Nitrite) 含量分析結果………………………………………………………95
圖12、 八週原兒茶酸和運動介入後之內皮細胞一氧化氮合成酶蛋白質表現量變化…………………………………………………96
圖13、八週原兒茶酸和運動介入後之胰島素受器蛋白質表現量變化………………………………………………………………97
圖14、 八週原兒茶酸和運動介入後之類胰島素生長因子-1受器蛋白質表現量變化…………………………………………………98
圖15、 八週原兒茶酸和運動介入後之丙二醛濃度變化……………99
圖16、 八週原兒茶酸和運動介入後過氧化氫酶酵素活性變……100

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