臺灣博碩士論文加值系統

脂質生合成酵素---Stearoyl-CoA desaturase (SCD) 於體內長期高血糖狀況扮演重要角色，其可被體內胰島素直接刺激增加表現。在 AD 過逝病患腦中發現有 SCD 表現顯著增加情形，且與認知功能測試分數呈現顯著負相關，顯示腦中 SCD 對於認知功能退化應扮演重要角色。本次實驗以高脂高果糖飲食誘發大鼠產生胰島素抗性及腦部認知功能障礙，並探討肝臟及腦中 SCD表現。本研究選用32隻6週齡大之 Wistar 大鼠，經分組後分為控制組、大豆油組及椰子油組。大豆油及椰子油組皆給予含大豆油或椰子油 39% 總熱量之脂質及含48% 總熱量之高果糖飲食。經誘發 20 週後以莫氏水迷宮給予認知功能測試並予以犧牲。由20週之血液生化數值顯示椰子油組血糖、果糖胺及胰島素均顯著高於控制組。莫氏水迷宮測試方面，第四天結果顯示椰子油組認知功能結果顯著低於控制組。進一步分析腦部皮質及肝臟中脂肪酸組成，結果顯示椰子油組於肝臟及大腦皮質中油酸含量及腦部皮質、海馬迴 SCD mRNA 表現均顯著高於控制組。故本次實驗結論大鼠肝及腦部 SCD 表現可被高飽和脂肪酸飲食誘發上升，且大鼠具高胰島素、血糖長期調控不良及認知功能障礙情形，而推測大鼠認知功能障礙與腦中 SCD 表現增加有關。

Stearoyl-CoA desaturase (SCD), one of the lipid synthesizing enzymes, plays an important role in hyperglycemia. Previous studies found that SCD expression increased in the brains of Alzheimer’s disease patients, and the expression of SCD was negatively correlated with cognitive score. The purpose of the present study was to investigate the effect of high fat high fructose diet (HFHF) on blood insulin resistance, brain cognitive impairment, SCD expression in rats. Wistar rats were 32 male, 6 weeks old and divided into 3 groups: control group (n=8), soybean oil group (n=12) and coconut oil group (n=12). Soybean oil group and coconut oil group were fed high fat (39% kcal) high fructose (48% kcal) diets with soybean oil or coconut oil separately for 20 weeks to induce blood insulin resistance. After 20 weeks, rats were given cognitive tests and sacrificed. Serum analysis at week 20 showed that compared with control group coconut oil group had higher blood glucose, insulin and fructosamine, which indicated hyperglycemia and insulin resistance. Day-4 Morris water maze result showed coconut oil group had lowest cognitive function compared with control groups. Western results showed that coconut oil group and soybean oil group had higher β-amyloid accumulation in brain cortex. In fatty acid composition, both cortex and liver had higher oleic acid contents in coconut group which indicated that the rats had higher SCD activity. In RT-PCR results, coconut oil groups had higher SCD mRNA expression in brain cortex and hippocampus compare with control group.In conclusion, SCD activity could be activated by a 20-week high saturated fatty acid high fructose diet, SCD metabolism related fatty acid content could also be changed. We also found cognitive impairment in rat brain, which may relevant with brain SCD activity.

目錄
中文摘要： VI
英文摘要 7
縮寫表 9
第一章 緒論 10
第二章、文獻回顧： 12
第一節、失智症 12
一、失智症盛行率： 12
二、阿茲海默症： 13
第二節、代謝症候群 15
一、 代謝症候群與認知功能障礙 16
二、糖尿病與認知功能障礙 16
三、高脂高果糖飲食與糖尿病 18
第三節、高脂高糖飲食與認知功能障礙 20
第四節、 飽和脂肪酸 21
一、高飽和脂肪酸攝取與代謝症候群 21
二、高飽和脂肪酸攝取與認知功能障礙 22
第五節、Stearoyl-coA desaturase (SCD) 23
一、SCD與脂質生合成 24
二、 SCD與飲食影響因子 24
三、周邊血液 SCD表現與胰島素訊息傳遞路徑之關係 26
四、腦部 SCD 與認知功能障礙 27
第三章、實驗假說與目的 28
第一節、實驗假說： 28
第二節、實驗目的： 29
第四章、實驗設計與方法： 30
第一節、實驗動物與實驗設計： 30
第二節、莫氏水迷宮試驗 (Morris Water Maze) 32
一、 水迷宮裝置 32
第三節、樣品採集與前處理 34
第四節、樣品分析方法 36
一、血液檢測方法 36
五、肝臟組織 43
六、SCD 測定 43
第七節、統計分析方法 46
第五章、實驗結果： 47
第一節 第0週時 大鼠血液生化數值 47
第二節 大鼠飲食及能量攝取情形 47
第三節 第 20 週時 大鼠血液生化數值 48
第四節 第 0 至 20 週 大鼠禁食血糖變化情形 48
第五節 第 20 週時 血清果糖胺分析 48
第六節 莫氏水迷宮 49
第七節 類澱粉樣蛋白堆積 49
第八節 肝臟脂質變性情形 50
第九節 大鼠海馬迴、皮質 SCD mRNA 表現 50
第十節 脂肪酸組成 51
第六章、討論 52
第一節 高脂高糖飲食與大鼠血糖調控之影響 52
第二節 高飽和脂肪酸高果糖飲食與大鼠體內脂質生成影響 55
第三節、高脂高果糖飲食與大鼠認知功能表現 57
第四節、高飽和脂肪酸攝取與認知功能表現 58
第五節、高脂高糖飲食對於類澱粉樣蛋白堆積影響 59
第六節、大鼠肝臟及腦部脂肪酸組成與 SCD mRNA 表現情形 60
第六章、結論 62
【參考文獻】 63
附錄一 72
附錄二 86

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