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研究生(外文):Huang, Chi-Zong
論文名稱(外文):Effects of Dioscorea Opposita Extracts on Blood Sugar and Lipid Regulation in Streptozotocin/nicotinamide-induced Diabetic Nice
指導教授(外文):Lee, Horng-MoWang, Shyang-Guang
口試委員(外文):Lee, Horng-MoWang, Shyang-GuangWu, Min-Tze
外文關鍵詞:Dioscorea oppositaMetabolic syndromeMyotube
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代謝症候群 (metabolic syndrome) 在近年來越來越受到重視,是由於現代大多數人往往過量飲食及缺乏運動,加上應酬飲酒過量等,久而久之這些原因就會造成人們過度肥胖、高血糖、高血脂、高血壓等,進而引發更多病症。為了改善代謝症候群及相關病發症的比率,透過將400多種中藥的酒精及水的萃取物進行檢驗並篩檢,找到了幾種中藥的水萃取物對於血糖的調控有明顯的效果,其中淮山藥(Dioscorea opposita) 對於血糖的調控效果顯著,而且淮山藥在古籍紀錄上可以發現搭配其他中藥一起服用,是具有緩和消渴症 (即:糖尿病) 的症狀,因此本研究對淮山藥的功效進行血糖調控及信息傳導路徑的探討。在本次研究中使用淮山藥萃取物對老鼠肌小管細胞 (C2C12 myotubes),及經nicotinamide和streptozotocin誘導的第二型糖尿病鼠(C57BL/6J)進行研究。結果發現經淮山藥作用的老鼠肌小管細胞內對於能量調控路經上的AMPK (AMP-activated protein kinase) 和ACC (acetyl-CoA carboxylase) 兩個蛋白質的磷酸化表現量上升,另一方面也發現在血糖調控路徑上的蛋白IRS1 (Insulin receptor substrate 1 )、Akt (Protein Kinase B) 的磷酸化表現量也上升。以上蛋白質的磷酸化表現量上升,表示對於能量活化及血糖的吸收是有幫助的,此外在小鼠的生化研究中,其體重、三酸甘油脂有明顯的下降,口服葡萄糖耐受性試驗中與對照組比起來結果也很顯著,最後犧牲後測量到內臟脂肪的減少,證實具有改善肥胖的現象。因此我們可以推斷懷山藥對於血糖的調控、抗肥胖是非常有效的,未來或許對於改善糖尿病是有幫助的。
The metabolic syndrome has received a great attention in recent years. The diet with high calories is considered as the risking factors for obesity, hypertension, high triglycerides and hyperglycemia. Dioscorea opposita had been reported to have beneficial effects on diabetes in ancient Chinese pharmacopoeia. We screened four hundred herbal extracts and found Dioscorea opposita extract could improve blood sugar level significantly. The purpose of this study was to investigate how Dioscorea opposite to regulate blood sugar. In cell experiments, the phosphorylations of AMPK (AMP-activated protein kinase) and ACC (acetyl-CoA carboxylase) were increased in differentiated C2C12 myotubes that were treated with aqua-extract of Dioscorea opposita. In addition, the phosphorylations of IRS1 (Insulin receptor substrate 1) and Akt (Protein Kinase B) were also up-regulated in cells. In animal study, the extract was shown to lower plasma triglyceride level, visceral fat, and weight in the STZ/Nicotinamide-induced-diabetic mice fed with high-fat diet. Furthermore, the extract also ameliorated hyperglycemia and improved glucose tolerance in mice. In conclusion, Dioscorea opposita could have beneficial effects on anti-hyperglycemic and anti-obesity.
中文摘要 I
Abstract III
目錄 IV
圖目錄 VII
縮寫表 IX
文獻檢索 10
代謝性症候群 (Metabolic syndrome) 10
糖尿病 (Diabetes mellitus) 11
AMP-activated protein kinase (AMPK) 12
Acetyl CoA carboxylase (ACC) 14
Insulin receptor substrate 1 (IRS-1) 16
研究動機和目的 17
實驗方法與材料 18
實驗材料 18
藥品試劑 18
常用儀器 19
常用溶液 21
實驗方法 23
C2C12細胞的培養 23
葡萄糖吸收測定試驗 ( [3H] Glucose uptake) 24
細胞活性測試 24
細胞蛋白質測定 (Protein assay) 25
西方墨點法 (Western blot) 26
動物實驗 (Studies of diabetic animal model) 27
統計方法 (Statistical data) 27
實驗結果 29
淮山藥萃取物對肌肉細胞吸收葡萄糖的影響 29
細胞存活率試驗 (cell viability) 29
淮山藥萃取物對提升胰島素敏感性的影響 30
淮山藥萃取物對AMPK和ACC的磷酸化之影響 30
淮山藥萃取物IRS-1和Akt的磷酸化之影響 31
淮山藥萃取物對糖尿病鼠脂肪堆積及葡萄糖耐受性之影響 32
討論 33
參考文獻 56

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