第一型糖尿病，也就是所謂的胰島素依賴型糖尿病(insulin-dependent diabetes mellitus)，約佔國內所有糖尿病患者的百分之三。第一型糖尿病是屬於自體免疫疾病，發病以孩童及青少年最常見。第一型糖尿病會促使循環血液中脂肪量上升，造成對肝臟的損害。目前對於糖尿病在肝臟造成的傷害，治療的方式仍然不多。　
有文獻指出，鎂離子可降低胰島素的阻抗並提高胰島素的分泌。而海洋深層水(deep-sea water)含有高含量的鎂，以及許多微量元素，能幫助並補充身體代謝運作所需的元素。因此，我們想要了解，海洋深層水對第一型糖尿病造成的肝臟受損是否具有保護效果。我們使用雄性大白鼠作為研究對象，誘導使其患有第一型糖尿病，再給予不同濃度海洋深層水與硫酸鎂離子，並且以western blot、gelatin zymography、TBARs、DPPH與GSH去分析當雄性大白鼠肝臟細胞在糖尿病的傷害下，所造成抗氧化活性、發炎、凋亡與自噬等路徑相關蛋白表現情形。實驗結果發現，海洋深層水可提高組織抗氧化能力並減少肝臟中MMP-9、iNOS、CRP等發炎因子的釋放，也可透過降低Toll-like receptor(TLR)經由MyD88所造成的發炎訊息路徑與自噬相關蛋白的表現。另外，海洋深層水也可藉由調控p53蛋白的表現進而抑制細胞凋亡的情形。因此，海洋深層水在未來也許可以提供在治療與預防第一型糖尿病的另一個選擇。

Insulin-dependent diabetes mellitus, so-called type 1 diabetes mellitus (DM), accounts for three percent of all diabetic patients in Taiwan. Type 1 DM is an autoimmune disease, which frequently occurs in children and adolescents. Type 1 DM will increase lipid level in blood and leads to liver abnormality. However, little is known about the treatment for liver damage caused by type 1 DM.
Male SD rats were adopted as experimental animals to induce type 1 DM by administrating STZ. Different concentrations of Deep-Sea-Water (DSW) were used to treat STZ-induced DM rats. Immunoblots, gelatin zymography, TBARs, DPPH and GSH assays were performed to investigate the anti-oxidant activity and the expressions of inflammation , apoptotic and autophagy proteins.
Our results show that DSW not only reduce the MMP-9、CRP and iNOS in liver, but also reduce the expression of Toll-like receptor (TLR), inflammation and autophagy proteins in MyD88 signaling pathways. Meanwhile, DSW may inhibits apoptosis through regulates p53/p21 express.
Herein we revealed the beneficial effects of DSW on type I DM rats and, therefore, reasonably conclude that DSW in the future may be useful to provide an alternative choice in treatment and prevention of type I DM.

目錄 I
中文摘要 1
Abstracts 2
壹、緒論 3
1-1.糖尿病簡介 3
1-2.糖尿病在醫學上研究 3
1-2-1.糖尿病的流行病學 3
1-2-2.糖尿病的症狀與致病機轉 4
1-3.糖尿病對肝臟影響 6
1-3-1.肝臟功能簡介 6
1-3-2. 肝臟病變 7
1-3-3. NAFLD發展過程中的相關因子簡介 7
1-3-4. NAFLD 的治療 9
1-4.海洋深層水(Deep-sea water)簡介 10
1-5.海洋深層水在醫學上的應用 11
貳、研究動機 12
叄、材料與方法 13
3-1. 實驗動物設計 13
3-1-1.實驗動物 13
3-2. 組織樣品 14
3-3. Catalase酵素活性分析(Catalase assay) 14
3-4. Total GSH assay 15
3-5. DPPH 自由基清除試驗 (DPPH assay) 15
3-6. 丙二醛含量測定 (TBARs assay) 16
3-7.蛋白質濃度分析 17
3-8. 西方墨點法(Western blotting , WB) 17
3-9. 明膠蛋白酵素電泳法(Gelatin zymography) 18
3-10. 統計方法 18
肆、結果 19
4-1.海洋深層水抑制糖尿病造成的脂質過氧化 19
4-2.海洋深層水抑制糖尿病誘導細胞發炎路徑指標蛋白與壓力相關蛋白的表現 19
4-3.海洋深層水減緩糖尿病所誘導NAFLD中細胞激素 20
4-4.海洋深層水降低 NAFLD 中免疫反應路徑的活化 21
4-5. 海洋深層水抑制糖尿病所誘導NAFLD中的細胞凋亡 22
4-6. 海洋深層水抑制糖尿病所誘導NAFLD中的細胞自噬 22
伍、討論 23
陸、參考文獻 25
柒、結果圖 31
Fig. 1 Deep-Sea Water attenuate the concentration of MDA in liver. 31
Fig. 2 Deep-Sea Water attenuate the concentration of DPPH in liver. 32
Fig. 3 Deep-Sea Water attenuate the concentration of GSH in liver. 33
Fig. 4 Deep-Sea Water attenuates the diabetes mellitus induced activity of MMP9. 34
Fig. 5 Deep-Sea Water attenuates the level of CRP. 35
Fig. 6 Deep-Sea Water attenuates the level of iNOS. 36
Fig. 7 Deep-Sea Water attenuates the level of HSP70. 37
Fig. 8 Deep-Sea Water attenuates the level of HSP90. 38
Fig. 9 Deep-Sea Water attenuates the level of TNF-α. 39
Fig. 10 Deep-Sea Water attenuates the level of IL1-β. 40
Fig. 11 Deep-Sea Water attenuates the level of IL-6. 41
Fig. 12 Deep-Sea Water attenuates the level of TLR4. 42
Fig. 13 Deep-Sea Water attenuates the level of TLR5. 43
Fig. 14 Deep-Sea Water attenuates the level of TLR7. 44
Fig. 15 Deep-Sea Water attenuates the level of TLR9. 45
Fig. 16 Deep-Sea Water attenuates the level of MyD88. 46
Fig. 17 Deep-Sea Water attenuates the phosphorylation of JNK. 47
Fig. 18 Deep-Sea Water attenuates the phosphorylation of ERK1/2. 48
Fig. 19 Deep-Sea Water attenuates the phosphorylation of P38. 49
Fig. 20 Deep-Sea Water attenuates the of IKK. 50
Fig. 21 Deep-Sea Water attenuates the level of NFκ-B. 51
Fig. 22 Deep-Sea Water attenuates the phosphorylation of PI3K. 52
Fig. 23 Deep-Sea Water attenuates the phosphorylation of AKT. 53
Fig. 24 Deep-Sea Water attenuates the phosphorylation of STAT3. 54
Fig. 25 Deep-Sea Water attenuates the level of p53. 55
Fig. 26 Deep-Sea Water attenuates the level of p21. 56
Fig. 27 Deep-Sea Water attenuates the level of cytochrome C. 57
Fig. 28 Deep-Sea Water attenuates the level of Apaf-1. 58
Fig. 29 Deep-Sea Water attenuates the activation of caspase-9. 59
Fig. 30 Deep-Sea Water attenuates the activation of caspase-3. 60
Fig. 31 Deep-Sea Water attenuates the level of Fas. 61
Fig. 32 Deep-Sea Water attenuates the activation of caspase-8. 62
Fig. 33 Deep-Sea Water attenuates the level of Atg3. 63
Fig. 34 Deep-Sea Water attenuates the level of Atg5. 64
Fig. 35 Deep-Sea Water attenuates the level of Atg7. 65
捌、論文架構圖 66

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