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研究生: 張瑀芳
Chang, Yu-Fang
論文名稱: 消渴草減輕高脂飼料及Streptozotocin誘導第二型糖尿病大鼠主動脈損傷之研究
Alleviative Effect of Ruellia tuberosa L. on Aorta Damage in High-Fat Diet plus Streptozotocin Induced Type 2 Diabetic Rats
指導教授: 沈賜川
Shen, Szu-Chuan
吳瑞碧
Wu, Swi-Bea
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: 2015
畢業學年度: 103
語文別: 中文
論文頁數: 119
中文關鍵詞: 第二型糖尿病消渴草主動脈損傷
英文關鍵詞: Type 2 diabetes mellitus, Ruellia tuberosa L., Aorta damage
論文種類: 學術論文
相關次數: 點閱:147下載:11
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  • 第二型糖尿病 (type 2 diabetes mellitus, Type 2 DM)因胰島素阻抗 (insulin resistance) 造成高胰島素血症 (hyperinsulinemia),而高胰島素血症與高葡萄糖血症 (hyperglycemia)為糖尿病血管病變的重要影響因子。糖尿病血管病變包含大血管 (macrovascular) 及小血管 (microvascular) 病變,其中大血管病變常見為動脈粥狀硬化症,易造成患者心臟疾病的發生並導致死亡。研究指出,消渴草 (Ruellia tuberosa L.) 具有抗氧化、抗發炎、抗癌等生理活性,亦可調節糖尿病大鼠之血脂平衡。本研究首先以小鼠肌肉C2C12細胞進行細胞試驗,結果顯示,在測試濃度(25、50、100、200、400及800μg/ml)下消渴草水及乙醇萃取物皆不具有細胞毒性;接著建立以TNF-α誘導胰島素阻抗細胞模式,發現在TNF-α 10ng/ml的濃度下,可有效誘導C2C12細胞產生胰島素阻抗;之後再以此細胞模式篩選具改善胰島素阻抗潛力之消渴草萃取物,結果顯示,不論是水或乙醇之消渴草萃取物,在濃度25μg/ml下即具有改善胰島素阻抗之C2C12細胞葡萄糖攝入之能力(p<0.05)。動物試驗結果顯示,每日餵食消渴草水及乙醇萃取物(劑量100與400mg/kg BW/day) 4週後可顯著改善高脂飼料及STZ誘導第二型糖尿病大鼠葡萄糖耐受能力。血液分析的結果顯示,消渴草萃取物可調節血脂及降低發炎反應相關因子,如:TNF-α, IL-6, VCAM-1, ICAM-1的含量;組織分析結果顯示,消渴草萃取物可增加抗氧化酵素SOD的活性及catalase的活性,並且降低發炎反應相關黏附因子MCP-1, VCAM-1的含量(p<0.05)。此外,消渴草萃取物可降低血管傷害相關因子,如:eNOS, ET-1, TF, vWF的含量(p<0.05),使其恢復至正常值。
    由上述結果推測,消渴草可以透過改善胰島素阻抗、發炎反應、氧化壓力等作用,而達到減輕高脂飼料及STZ誘導第二型糖尿病大鼠主動脈損傷之效果。

    The diabetes mellitus patients are mainly Type 2 DM, which is characterized by hyperinsulinemia resulted from insulin resistance. Researches indicated that hyperinsulinemia and hyperglycemia are important factors in diabetic vascular disease, including macrovascular and microvascular disease. Ruellia tuberosa L. (RTL) was used as folklore medicine for diabetes in Asia as well as Taiwan. RTL was previously reported to exhibit anti-oxidant, anti-inflammatory and anti-cancer abilities. The mouse muscle myotube C2C12 cells were treated with 10ng/mL TNF-α to induce insulin resistance. These cells were subsequently co-incubated with water or ethanol extract from RTL. The uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in insulin-resistant C2C12 cells was used as a platform for screening extracts from RTL with the anti-hyperglycemic potential. The protective effect of RTL extract on aorta damage in high-fat diet plus streptozotocin induced T2DM rats was further investigated. The results show that both water and ethanol extracts from RTL (25μg/ml) significantly improves the glucose uptake in insulin-resistant C2C12 cells (p< 0.05). Both water and ethanol extracts from RTL (100 and 400mg/kg BW/day) significantly decreases plasma glucose level, decreases the concents of serum TNF-α, IL-6 and VCAM-1. The enzyme-linked immunosorbent analysis suggested that RTL decreases the contents of MCP-1, VCAM-1 and recovers the contents of eNOS, ET-1, TF and vWF in the aortas of diabetic rats.
    The above observations suggested that RTL may alleviate the aorta damage via improving insulin resistance, inflammation and oxidative stress in high-fat diet plus STZ induced T2DM rats.

    中文摘要 I Abstract II 目錄 III 圖次 VII 表次 IX 第一章 前言 1 第二章 文獻回顧 3 第一節 糖尿病 3 一、 糖尿病簡介 3 二、 糖尿病流行病學 3 三、 糖尿病分類 5 四、 糖尿病診斷標準 9 五、 成人糖尿病血糖控制建議 10 六、 胰島素抗性致敏劑(Thiazolidinediones, TZDs)藥物 11 第二節 胰島素阻抗 13 一、 胰島素阻抗 13 二、 胰島素阻抗之機制 13 三、 骨骼肌細胞胰島素阻抗之機制 15 第三節 消渴草植物之相關研究 17 一、 台灣常見治療糖尿病之植物與相關研究 17 二、 消渴草 (Ruellia tuberosa Linn., RTL) 簡介 17 三、 消渴草植物之相關研究 18 第四節 第二型糖尿病與心血管疾病 20 一、 第二型糖尿病與心血管疾病相關研究 20 二、 連結第二型糖尿病與心血管疾病的可能機制 21 第三章 研究動機與目的及實驗架構 29 第一節 研究動機與目的 29 第二節 實驗架構 30 第四章 消渴草萃取物於胰島素阻抗細胞之葡萄糖攝入探討 31 第一節 實驗材料 31 一、 實驗樣品來源 31 二、 實驗細胞 31 三、 實驗藥品與試劑 31 四、 儀器設備 32 第二節 實驗步驟與方法 34 一、 消渴草水萃取物及乙醇萃取物之製備 34 二、 實驗樣品配製 34 三、 實驗藥品配製 34 四、 小鼠肌肉細胞 C2C12 之保存與培養 35 五、 C2C12 細胞由纖維母細胞 (myoblast) 分化為管狀細胞 (myotube) 35 六、 C2C12 細胞生長存活率試驗 (MTT assay) 36 七、 C2C12 細胞對2-NBDG 染劑之攝入作用 36 八、 細胞蛋白質定量 38 九、 TNF-α 誘導 C2C12 細胞胰島素阻抗 38 十、 消渴草水及乙醇萃取物對具胰島素阻抗之 C2C12 細胞葡萄糖攝入作用 39 十一、 統計分析 39 第三節 結果 40 一、 消渴草水及乙醇萃取物對 C2C12 細胞生長存活率 (cell viability)的影響 40 二、 C2C12 細胞對 2-NBDG 染劑攝入之條件探討 40 三、 TNF-α 誘導 C2C12 細胞胰島素阻抗模式之建立 41 四、 消渴草水及乙醇萃取物對具胰島素阻抗之 C2C12 細胞葡萄糖攝入作用之影響 41 第四節 討論 42 一、 消渴草水及乙醇萃取物對 C2C12 細胞生長存活率 (cell viability)的影響 42 二、 C2C12 細胞對 2-NBDG 染劑攝入之影響 42 三、 TNF-α 誘導 C2C12 細胞胰島素阻抗之影響 43 四、 消渴草水及乙醇萃取物對具胰島素阻抗之 C2C12 細胞葡萄糖攝入作用之影響 43 第五節 結論 45 第五章 消渴草減輕高脂飼料及STZ誘導第二型糖尿病大鼠主動脈損傷之研究 52 第一節 實驗材料 52 一、 實驗樣品來源 52 二、 實驗動物 52 三、 實驗動物墊料 52 四、 實驗動物飼料 52 五、 實驗藥品與試劑 53 六、 儀器設備 55 第二節 實驗步驟與方法 57 一、 實驗樣品配製 57 二、 實驗藥品配製 57 三、 實驗動物飼養 58 四、 實驗動物誘導及分組 58 五、 試驗方法 59 六、 統計分析 70 第三節 結果 71 一、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠生理、生化數值之影響 71 二、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈病理切片觀察 75 三、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈抗氧化酵素活性之影響 76 四、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈發炎反應相關黏附因子之影響 77 五、 消渴草萃取物對減輕高脂飼料及STZ誘導第二型糖尿病大鼠主動脈損傷的影響 77 第四節 討論 80 一、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠生理、生化數值之影響 80 二、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈病理切片之影響 83 三、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈抗氧化酵素 SOD表現與Catalase活性之影響 85 四、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈發炎反應相關黏附因子MCP-1、VCAM-1之影響 85 五、 消渴草萃取物對高脂飼料及STZ誘導第二型糖尿病大鼠主動脈損傷相關因子的影響 86 第五節 結論 91 第六章 參考文獻 114

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