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研究生: 林士翔
Lin, Shih-Xiang
論文名稱: α-硫辛酸改善高脂飲食及STZ誘導高胰島血症大鼠肌肉萎縮之研究
Effect of α-lipoic acid on muscle atrophy in hyperinsulinemic rats induced by high-fat diet plus streptozotocin
指導教授: 沈賜川
Shen, Szu-Chuan
吳瑞碧
Wu, JamesSwi-Bea
丁俞文
Ting, Yu-Wen
學位類別: 碩士
Master
系所名稱: 人類發展與家庭學系
Department of Human Development and Family Studies
論文出版年: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 88
中文關鍵詞: 糖尿病肌肉萎縮胰島素阻抗硫辛酸抗氧化劑
英文關鍵詞: T2DM, muscle atrophy, insulin resistance, alpha-lipoic acid, Antioxidants
DOI URL: http://doi.org/10.6345/THE.NTNU.DHDFS.036.2018.A06
論文種類: 學術論文
相關次數: 點閱:240下載:8
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  • 流行病學研究顯示糖尿病患者罹患肌少症(sarcopenia)的比率比一般人高出三倍。第2型糖尿病的蛋白質合成和降解不平衡會造成患者肌肉萎縮,而肌肉萎縮是導致肌少症的主要症狀之一。文獻指出,高脂肪飲食會誘導周邊組織,例如肌肉產生氧化壓力與胰島素阻抗(insulin resistance)。胰島素阻抗被認為是影響肌肉蛋白流失的主要因素之一,因此推測其與肌肉萎縮之發生有關。α-硫辛酸(ALA)是一種生物抗氧化劑,研究指出其可緩解胰島素抵抗。
    本研究的目的是探討ALA對HFD與鏈脲佐菌素(STZ)誘導的高胰島素血症大鼠肌肉萎縮的影響及其機制。雄性Wistar大鼠餵食HFD 4週後以腹膜內注射STZ,然後連續8週給予HFD以誘導高胰島素血症,之後給予高胰島素血症大鼠ALA每日一次,連續13週。大鼠犧牲後摘取比目魚肌並稱重,另以H&E染色觀察肌纖維的形態學,並使用西方墨點法分析胰島素信號傳遞、發炎、肌肉再生與分解相關的蛋白質表現。
    結果顯示,高脂飲食大鼠之比目魚肌肌肉量顯著增加,而H&E染色分析顯示,ALA處理的高胰島素血症大鼠肌肉纖維截面長度顯著增加48.6%,表示ALA處理可以維持較好的肌肉纖維。Western bolt分析顯示,ALA上調高胰島素血症大鼠比目魚肌胰島素信號傳遞相關蛋白質和肌肉再生相關蛋白質的表現,其同時也下調了發炎與肌肉分解相關蛋白質之表現。
    由以上結果顯示,ALA具有改善糖尿病患者肌肉中胰島素阻抗和肌肉萎縮的潛力,期望未來ALA可以開發為治療糖尿病引起的肌肉萎縮的藥物或膳食補充劑。

    Epidemiological studies revealed three fold higher risk of sarcopenia in diabetes mellitus (DM) patients. One of the symptoms of sarcopenia , muscle atrophy,is caused by an imbalance in protein synthesis and degradation which can be triggered by Type 2 Diabetes Mellitus. High fat diet (HFD) was reported to induce oxidative stress and insulin resistance in peripheral tissues, including muscle, of animals. Alpha-lipoic acid (ALA) which is a potent biological antioxidant would alleviate insulin resistance.
    The purpose of this study was to investigate the effects of ALA on alleviate muscle atrophy in HFD plus streptozotocin (STZ)-induced hyperinsulinemic rats and to explore the underlying mechanisms. The male Wistar rats fed HFD for 4 weeks were intraperitoneally (ip) injected STZ and then served HFD continuously for 8 weeks to induce hyperinsulinemia. The hyperinsulinemic rats were then orally administered with ALA for 13 weeks. After sacrifice, the soleus muscle was weighed and H&E staining was performed for morphological observation of muscle fibers. The protein expression of insulin signaling, inflammation, muscle regeneration and catabolic related signal proteins were analyzed by western blotting.
    The results show that administration of ALA significantly increased soleus muscle mass in hyperinsulinemic rats. H&E staining image analysis reveals that muscle fibers significantly increased by 48.6% in ALA-treated hyperinsulinemic rats. The western bolt analysis indicates that ALA up-regulated expression of insulin signaling、muscle regeneration related proteins, and down-regulated expression of inflammation、muscle protein breakdown related proteins.
    Above observations demonstrates that ALA has the potential on improving the insulin resistance and muscle atrophy in muscle of DM patients. In the future, ALA may become a possible alternative therapy to treat muscle atrophy caused by diabetes.

    第一章. 前言 1 第二章. 文獻回顧 2 第一節. 糖尿病 2 一、 糖尿病定義及其合併症 2 二、 糖尿病流行病學 2 三、 糖尿病分類 3 四、 糖尿病診斷 5 第二節. 胰島素阻抗 6 一、 胰島素簡介 6 二、 胰島素訊息傳遞及作用 6 三、 胰島素阻抗簡介 8 四、 肥胖與胰島素阻抗形成 8 五、 高胰島素血症與胰島素阻抗 10 第三節. 氧化壓力與發炎 11 一、 氧化壓力 11 二、 發炎路徑 11 三、 胰島素阻抗與發炎 13 第四節. 肌少症 14 一、 肌少症簡介 14 二、 肌少症流行病學 14 三、 肌少症與高胰島素血症的關聯性 15 四、 肌少症、肥胖與胰島素阻抗的關聯 16 第五節. 肌肉生成 17 一、 骨骼肌分類 17 二、 肌肉生成途徑 18 三、 胰島素阻抗與肌肉再生 21 第六節. 肌肉分解 22 一、 肌肉分解路徑 22 二、 胰島素阻抗與肌肉分解 23 第七節. 硫辛酸 25 一、 硫辛酸簡介 25 二、 硫辛酸與氧化壓力 26 三、 硫辛酸與胰島素阻抗 26 第三章. 實驗目的與架構 27 第一節. 實驗動機與目的 27 第二節. 實驗架構 28 第四章. 實驗材料與方法 29 第一節. 樣品製備之材料 29 一、 實驗材料 29 二、 實驗動物來源 32 三、 實驗動物飼料 32 第二節. 試驗方法 33 一、 實驗樣品配置 33 二、 實驗藥品配置 33 三、 實驗動物誘導及分組 34 四、 試驗方法 35 五、 儀器設備 43 六、 統計分析 44 第五章. 實驗結果 45 第一節. α –硫辛酸對高脂肪飲食併合STZ藥物誘導高胰島素血症大鼠血液生理生化值之影響 45 一、 體重與飲水、食物攝取量 45 二、 血液血糖、胰島素值 45 三、 血液生化值 46 第二節. α –硫辛酸對高脂肪飲食併合STZ藥物誘導高胰島素血症大鼠肌肉發炎與肌肉纖維長度之影響 50 一、 肌肉腫瘤壞死因子-α值 50 二、 肌肉質量與纖維長度 50 第三節. α –硫辛酸對高脂肪飲食併合STZ藥物誘導高胰島素血症大鼠細胞傳訊蛋白質之影響 56 一、 胰島素傳訊路徑 56 二、 發炎相關路徑 56 三、 肌肉再生路徑 57 四、 肌肉分解路徑 57 第六章. 討論 68 第一節. 生理血液生化 68 第二節. 肌肉纖維長度與質量 69 第三節. 胰島素傳訊系統 70 第四節. 發炎與相關傳訊系統 71 第五節. 肌肉相關傳訊系統 72 第六節. 硫辛酸減緩高胰島素血症大鼠肌肉萎縮的可能機制 73 第七章. 結論 76 第八章. 附錄 77 第九章. 參考資料 81

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