第2型糖尿病患者血糖控制不良時，會造成全身性高血糖，而長期高血糖會促使過多的葡萄糖走向多元醇路徑來代謝，增加糖化終產物的堆積，導致組織的傷害。香瓜茄為茄科茄屬植物，台灣產地大多位於澎湖，本實驗室先前以BALB/c小鼠誘發成第2型糖尿病，已發現香瓜茄對第2型糖尿病具有延緩體內傷害及多元醇路徑之影響。因此本實驗室更進一步利用leptin receptor基因變異的db/db老鼠，觀察香瓜茄對第2型糖尿病的影響。db/db小鼠分別餵食1%和2%香瓜茄水萃物八週，取血液、肝臟、腎臟、胰臟等臟器進行實驗分析。結果顯示db/db小鼠餵食不同劑量的香瓜茄水萃物八週後，胰島素阻抗性有顯著的改善；在血脂方面，血清中cholesterol、TG、free fatty acid顯著下降，肝臟DGAT-2和副睪脂肪DGAT-1基因表現也顯著下降；在抗氧化方面，肝臟、腎臟、胰臟及坐骨神經也都有顯著上升；在多元醇路徑方面，腎臟、胰臟、紅血球及坐骨神經的多元醇路徑關鍵酵素Aldose reductase比活性和終產物Fructose的堆積有下降的情形；在發炎方面，腎臟TGF-β1基因表現量與纖維網狀蛋白含量都有減；在組織切片方面，腎臟及坐骨神經有保護作用。因此根據本研究顯示香瓜茄水萃物可降低db/db小鼠體內氧化壓力及糖化作用，進而可以延緩第2型糖尿病的併發症發生。

Solanum muricatum Ait (pepino) is a popular plant food in Penghu island, Taiwan. Our previous study has reported that the aqueous extract from pepino was able to improve antioxidant defense and polyol pathway in streptozotocin induced type 2 diabetic BALB/c mice. Therefore, we further use the leptin receptor gene mutated db/db mice to investigate the effects of pepino aqueous extract on type 2 diabetes.
Db/db mice were fed by 1 or 2% aqueous pepino for eight weeks. The serum and tissues were collected to analyze. Results showed that pepino intake improved insulin resistance and decreased resistin gene expression. This extract inhibited DGAT-2 gene expression in liver, DGAT-1 gene expression in adipose tissue, reduced lipid synthesis, lowered serum cholesterol, triglyceride and free fatty acids. In addition, this extract also reduced malondialdehyde (MDA); retained glutathione (GSH), glutathione peroxidase (GPx) in liver, kidney, pancreas and sciatic nerve, attenuated oxidative damage. The activity of aldose reductase, a key enzyme in polyol pathway, decreased in kidney, pancreas, erythrocyte and sciatic nerve. Also, the fructose and N-ε-carboxymethyl-lysine (CML) levels were lowered in these organs. On the other hand, this extract inhibited TGF-β1 gene expression and reduced fibronectin level in kidney, and decreased inflammatory stress. These results suggest that pepino aqueous extract could delay progression of type 2 diabetic complications by decreasing oxidative stress, glycosylation and inflammatory response.

目錄………………………………………………………………………………….…I
圖表目次………………………………………………………………………..……IV
中文摘要…………………………………………………………………………..…VI
英文摘要………………………………………………………………...….………VII
第一章、前言………………………………………………………………………..1
第二章、文獻探討……………………………………………………………………2
一、糖尿病簡介………………………………………………………………………2
(一)定義……………………………………………………………………………….2
(二)診斷標準………………………………………………………………………….2
(三)分類………………………………………………………………………..2
(四)症狀…………………………………………………………………………….....4
(五)併發症…………………………………………………………………………….6
二、糖尿病與氧化壓力………………………………………………………………7
三、糖尿病與多元醇路徑……………………………………………………………8
四、香瓜茄……………………………………………………………………………10
五、db/db小鼠模式…………………………………………………………………12
第三章、研究目的……………………………………………………………………14
第四章、材料與方法…………………………………………………………………15
一、實驗材料與儀器…………………………………………………………………15
(一)香瓜茄…………………………………………………………………………15
(二)實驗動物………………………………………………………………………15
(三)化學藥品………………………………………………………………………15
(四)儀器設備………………………………………………………………………17
二、實驗設計…………………………………………………………………………17
(一)香瓜茄水萃物飼料製備………………………………………………………17
(二)動物模式………………………………………………………………………18
(三)樣本收集………………………………………………………………………18
三、實驗分析方法……………………………………………………………………19
(一)血糖測定………………………………………………………………………19
(二)口服葡萄糖耐受試驗(Oral Glucose Tolerance Test) …………………………19
(三)、胰島素(Insulin)含量測定……………………………………………………20
(四)胰島素阻抗(Homeostasis Model Assessment-insulin resistance；HOMA-IR)…20
(五)總蛋白濃度測定………………………………………………………………21
(六)脂質過氧化 (Malondialdehyde，MDA)測定…………………………………21
(七)、麩胱苷肽過氧化酶(Glutathione peroxidase；GPx)比活性測定………………22
(八)醛糖還原酶(Aldose reductase；AR)比活性測定………………………………23
(九)總抗氧化能力(Trolox equivalent antioxidant capacity)測定…………………24
(十)三酸甘油酯(Triglycerides)濃度測定…………………………………………24
(十一)膽固醇(Cholesterol)濃度測定………………………………………………25
(十二)纖維網狀蛋白(Fibronectin)含量測定以西方墨點法(Western blot)………26
(十三)反轉錄聚合酶連鎖反應……………………………………………………26
(十四)麩胱甘肽(Glutathione；GSH)含量測定………………………………………29
(十五)羧甲基化離胺酸(N-ε-carboxymethyl-lysine；CML)含量測定……………30
(十六)果糖（Fructose）含量測定……………………………………………………31
(十七)游離脂肪酸（Free Fatty Acid）含量測定……………………………………31
(十八)統計分析……………………………………………………………………32
第五章、實驗結果……………………………………………………………………33
一、餵食八週1％、2％香瓜茄水萃物對於第2型糖尿病db/db小鼠生理之影響………………………………………………………………………………33
二、餵食八週1％、2％香瓜茄水萃物對於第二型糖尿病db/db小鼠血糖、胰島
素阻抗之影響…………….…………………………………………………………33
三、餵食八週1％、2％香瓜茄水萃物對於第二型糖尿病db/db小鼠體內氧化壓
力之影響……………………………………………………………………………34
四、餵食八週1％、2％香瓜茄水萃物對於第二型糖尿病db/db小鼠體內多元醇
路徑之影響…………………………………………………………………………35
五、餵食八週1％、2％香瓜茄水萃物對於第二型糖尿病db/db小鼠體內血脂與
副睪脂肪重之影響…………………………………………………………………36
六、餵食八週1％、2％香瓜茄水萃物對於第二型糖尿病db/db小鼠腎臟及坐骨神 經之影響…………………………………………….……………………………..36
第六章、討論…………………………………………………………………………66
第七章、結論…………………………………………………………………………73
第八章、參考文獻……………………………………………………………………74

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