臺灣博碩士論文加值系統

白花蛇舌草 (Hedyotis diffusa, HD) 為台灣民間常用之中草藥，具有抗氧化、抗腫瘤及免疫調節等特性。研究顯示白花蛇舌草內含有齊墩果酸 (oleanolic acid) 與熊果酸 (ursolic acid) 兩種主成分，而此兩種多酚在糖尿病的相關實驗中可藉由抑制糖質新生達到降血糖的效果，故本研究欲探討白花蛇舌草對鏈脲佐菌素 (streptozotocin, STZ) 結合菸鹼醯胺所誘發糖尿病大鼠之降血糖作用。將白花蛇舌草以不同溶劑 (水、50%乙醇、95%乙醇) 萃取，測定其抑制肝臟糖質新生之關鍵酵素 (glucose-6-phosphatase (G-6-Pase)、phosphoenolpyruvate carboxykinase (PEPCK) ) 活性，發現95%乙醇萃取物之抑制效果較佳。選擇此萃取方式進行動物實驗，將Wistar大鼠隨機分成五組，分別為控制組、糖尿病組、1%與3%白花蛇舌草組及正控制組（metformin）。除控制組外，其餘以STZ結合菸鹼醯胺合併高脂飼料誘發第二型糖尿病，經過四週後顯示，白花蛇舌草萃取物可顯著降低餐後一小時血糖濃度、在口服葡萄糖耐受測試 (OGTT) 中降低第60分鐘的血糖值，以及抑制糖新生關鍵酵素(G-6-Pase、fructose 1,6-bisphosphatase、PEPCK) 之活性。在血脂方面，給與白花蛇舌草萃取物可顯著降低血清中三酸甘油酯及總膽固醇的濃度，並可降低血清中TBARS含量。綜合上述，白花蛇舌草萃取物在體外可抑制糖新生關鍵酵素之活性，於動物實驗中可藉由降低肝臟糖質新生作用，達到改善第二型糖尿病餐後血糖的效果，並具有降低血脂之作用。

Hedyotis diffusa (HD) is a well-known Chinese folk medicine. Previous research has shown that HD has many potentially beneficial health effects including antioxidant, anti-tumor and immunomodulatory activities. Recent studies found that oleanolic acid and ursolic acid, the main phenolic compounds in HD, can reduce blood glucose by inhibiting gluconeogenesis in diabetic rats. Therefore, the present study investigated the hypoglycemic effects of Hedyotis diffusa in streptozotocin-nicotinamide-induced diabetic rats. The HD extracts derived from various solvents (hot water, 50% ethanol and 95% ethanol) were used to inhibit the enzyme activities (including glucose-6-phosphatase, G-6-pase and phosphoenolpyruvate carboxykinase, PEPCK) in gluconeogenesis were assayed. The results showed that HD extracts of 95% ethanol possessed the best inhibitory capacities of key enzymes in gluconeogenesis and therefore was chosen for the subsequent animal experiment. Wistar rats were randomly divided into control group, diabetic group, low- or high-dosage of HD extracts (1%, 3% extracts in diet, respectively) and positive control group (metformin). In addition to control group, rats were induced to develop type 2 diabetes mellitus by intraperitoneal injection of streptozotocin- nicotinamide in combination with high-fat diet. After four weeks, the results showed that ethanol extracts from HD significantly decreased postprandial blood glucose, blood glucose levels after oral glucose tolerance test (OGTT) at the 60th minute, and inhibited enzyme activities in gluconeogenesis, including G-6-Pase, fructose 1,6-bisphosphatase and PEPCK. In addition, diabetic rats treated with HD extracts displayed significantly decreased triacylglycerol, total cholesterol and thiobarbituric acid reactive substances (TBARS) content in serum. In conclusion, the 95% ethanol extracts of HD significantly inhibit enzyme activities in gluconeogenesis in vitro and improve postprandial blood glucose by inhibiting gluconeogenesis and hypolipidemia in type 2 diabetic rats.

目錄 頁次
中文摘要.........................................................................................................................Ⅰ
英文摘要.........................................................................................................................Ⅱ
致謝.................................................................................................................................Ⅲ
目錄.................................................................................................................................Ⅳ
表目錄.............................................................................................................................Ⅶ
圖目錄.............................................................................................................................Ⅷ
附表及附圖目錄.............................................................................................................Ⅹ
壹、 緒言......................................................................................................................1
貳、 文獻回顧
一、糖尿病 (Diabetes mellitus)
(一) 糖尿病之成因及分類...........................................................................2
(二) 糖尿病之診斷標準...............................................................................3
(三) 餐後高血糖與第二型糖尿病之相關性...............................................5
(四) 肥胖與胰島素阻抗及第二型糖尿病之相關性...................................6
(五) 糖尿病之治療.......................................................................................7
(六) 二甲雙胍藥物 (Metformin) 治療糖尿病之相關機制.......................8
二、 肝臟中葡萄糖轉運與代謝途徑
(一) 己糖激酶...............................................................................................9
(二) 糖質新生作用.....................................................................................10
三、白花蛇舌草 (Hedyotis diffusa)
(一) 白花蛇舌草之簡介.............................................................................11
(二) 白花蛇舌草之生理活性.....................................................................11
(三) 白花蛇舌草成分與糖尿病關係之探討.............................................12
四、鏈脲佐菌素結合菸鹼醯胺誘發糖尿病鼠之動物模式
(一) 鏈脲佐菌素 (STZ) 誘導糖尿病之相關機制....................................16
(二) 以STZ結合菸鹼醯胺（nicotinamide, NA）誘發糖尿病之機制與原
理...........................................................................................................17
參、 實驗材料與方法
一、實驗目的.........................................................................................................19
二、設計架構.........................................................................................................19
三、材料與器材.....................................................................................................21
四、實驗方法.........................................................................................................25
(一)實驗I：不同溶劑之白花蛇舌草萃取物對糖質新生相關酵素活性能力
之比較.......................................................................................25
(二)實驗Ⅱ：白花蛇舌草萃取物對STZ-NA誘導糖尿病大鼠之影響.....26
(三)實驗Ⅲ：白花蛇舌草之機能性成分分析..............................................33
五、統計分析.........................................................................................................33
肆、 結果.....................................................................................................................34
一、 實驗 I:不同溶劑之白花蛇舌草萃取物抑制糖質新生相關酵素活性能力之比較
(一)以不同溶劑萃取白花蛇舌草對葡萄糖六磷酸酶 (G-6-Pase) 活性之影
響.............................................................................................................34
(二)以不同溶劑萃取白花蛇舌草對PEPCK活性之影響............................34
二、實驗Ⅱ:白花蛇舌草萃取物對STZ-NA誘導糖尿病大鼠之糖代謝影響
(一) 體重及攝食量之變化.............................................................................34
(二) 空腹、餐後血糖與胰島素、HOMA-IR值之影響..............................35
(三) 口服葡萄糖耐受試驗 (OGTT) 血糖濃度之變化...............................36
(四) 糖質新生相關酵素之活性.....................................................................36
(五) 血清中果糖胺濃度之影響.....................................................................37
(六) 血清、肝臟中總抗氧化能力及脂質過氧化程度.................................37
(七) 血清總膽固醇與三酸甘油酯之濃度.....................................................38
三、實驗Ⅲ:白花蛇舌草之機能性成分分析........................................................38
伍、 討論.....................................................................................................................39
陸、 結論.....................................................................................................................51
柒、 參考文獻.............................................................................................................73

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