臺灣博碩士論文加值系統

現行流行病學研究統計指出，多種危險因子與第二型糖尿病的發病有關，其中肥胖是一項最常見的因素，並且伴隨著代謝症候群的發生。根據實驗室之前的研究，龍鬚菜水萃物(water extracts of Sechium edule shoots, SWE)可以有效抑制油酸所誘導肝臟脂肪合成和脂肪分解增加。因此，本研究的目的是探討SWE對高油脂飲食（High fat diet, HFD）配合低劑量Streptozotocin (STZ)所誘發出的高血脂高血糖的糖尿病大鼠的抑制作用。將大鼠隨機分為4組：control組、HFD + STZ組、HFD + STZ + SWE0.5％組、HFD + STZ + SWE1.0％組。確認施打STZ之組別其血糖> 200 mg/dl後，即可開始加藥進行八週的試驗，於犧牲後將血清和組織進行分析。結果發現SWE0.5%及1.0%組的血糖有明顯比HFD + STZ組下降約20%。然而，血清中三酸甘油酯和及總膽固醇表現量並無受顯著影響。從組織切片做觀察，利用Hematoxylin-Eosin stain (H&E stain)及油紅(Oil red O stain)染色分析，從加藥組與誘導組做比較，觀察到餵食SWE可明顯改善肝臟中脂肪泡的堆積。另外，腎臟組織利用H&E、Periodic Acid-Schiff stain和Masson氏染色分析，結果表明，SWE亦可以避免由高血糖所引起的腎間質增生、醣質推積以及膠原蛋白增生。整體而言，本篇實驗證明在由高油脂飲食誘發之第二型糖尿病大鼠模式上，透過龍鬚菜萃取物的添加，可以穩定血液中葡萄糖的表現量，亦可以減緩高血糖所引起的副病變傷害，未來對於在代謝症候群的治療上亦有很大的幫助。

Epidemiological studies indicate that obesity is important risk factors for several diseases, particularly type 2 diabetes. According to our previous study, the water extracts of Sechium edule shoots (SWE) inhibits oleic acid-induced hepatic lipogenesis and increases lipolysis. Therefore, the aim of this study is to investigate the anti-diabetic effects of SWE on high fat diet (HFD)-induced diabetes mellitus (DM). Sprague-Dawley (SD) rats were fed with HFD and then followed by low dose of streptozotocin (STZ) intraperitoneal injection result in type 2 diabetes. Rats were divided into 4 group: control group , HFD+STZ group , HFD+STZ+SWE0.5% group , HFD+STZ+SWE1.0% group. After completing the induction (mimic DM blood sugar level > 200 mg/dl), the animals were given 0.5% or 1% of SWE for further 8 weeks, and then the serum and tissue were collected to analyze. The blood glucose level in 0.5% and 1% SWE-treated groups were substantially reduced 20% as compared to the HFD+STZ group. The kidney tissues were analyzed by using Hematoxylin-Eosin stain, Periodic Acid-Schiff stain and Masson''s staining. The results show that SWE decrease mesangial matrix expansion in the glomerular, accumulation of saccharide and collagen fiber expansion. Collectively, these data providence evidence that when supplemented SWE to a diet, can improve glucose homeostasis and improved insulin sensitivity in insulin resistant induced rats. This result suggests that Sechium edule shoots has potential to influence the development of metabolic syndrome.

目錄 I
縮寫檢索表 III
中文摘要 IV
Abstract VI
一、文獻探討 1
1.1. 糖尿病簡介 1
1.1.1. 糖尿病之定義與診斷標準 1
1.1.2. 糖尿病之分類 2
1.1.3. 糖尿病之症狀 5
1.2. 糖尿病之併發症 9
1.2.1. 急性併發症 9
1.2.2. 慢性併發症 10
1.3. 調控脂質代謝相關蛋白 13
1.3.1. AMPK(AMP-activated protein kinase) 13
1.3.2. FAS(Fatty acid synthase) 14
1.3.3. HMGCoR(HMG CoA reductase) 14
1.3.4. SREBPs(Sterol regulatory element-binding proteins) 15
1.3.5. CPT-1(Carnitine palmitoyl transferase I) 16
1.4. 糖尿病相關機制 18
1.4.1. 糖尿病與氧化壓力(oxidative stress) 18
1.4.2. 糖尿病與多元醇路徑(polyol pathway) 20
1.4.3. 糖尿病與糖化終產物(Advanced glycation end-product, AGE) 21
1.4.4. 糖尿病與蛋白激酶C路徑(Protein kinase C, PKC) 23
1.5. 腎臟與糖尿病腎病變 24
1.5.1. 腎臟之簡介 24
1.5.2. 糖尿病腎病變之病程[20, 52] 25
1.6. 糖尿病動物模式 27
1.6.1. 自發型 27
1.6.2. 誘發型 27
1.7. 龍鬚菜簡介 31
1.7.1. 龍鬚菜背景及型態 31
1.7.2. 產期及產地 31
1.7.3. 龍鬚菜之所含成份 31
1.7.4. 功效及應用 32
二、研究動機 33
三、實驗模式與架構 34
四、實驗材料與方法 35
4.1. 實驗材料及設備 35
4.2. 實驗方法 38
4.2.1. 龍鬚菜萃取物的製備 38
4.2.2. 實驗動物 38
4.2.3. 第二型糖尿病動物模式建立與實驗設計 38
4.2.4. 飼料組成與配置 39
4.2.5. 動物血糖之檢測 40
4.2.6. 動物血漿中胰島素濃度之分析 40
4.2.7. 動物檢體之收集 40
4.2.8. 西方點墨法 41
4.2.9. 組織病理切片之染色 43
4.2.10. 血清中生化值分析 46
4.2.11. 血液中酵素測定 47
4.2.12. 肝臟中脂質觀察 48
4.2.13. 統計分析 49
五、實驗結果 50
5.1. 誘發第二型糖尿病之實驗動物模式 50
5.2. SWE具有穩定第二型糖尿病大鼠血糖代謝之的效果 50
5.2.1. 觀察八週實驗大鼠血糖變化值 50
5.2.2. 觀察八週實驗大鼠胰島素變化值 51
5.2.3. 觀察大鼠HbA1c表現量 51
5.3. SWE對高脂飼料誘導之第二型糖尿病大鼠之臟器重量影響 52
5.3.1. 觀察SWE對大鼠肝臟重量的影響 52
5.3.2. 觀察SWE對大鼠腎臟重量的影響 52
5.4. SWE對於第二型糖尿病大鼠血清生化值之影響 53
5.4.1. 脂質代謝指標 53
5.4.2. 肝功能指標 53
5.4.3. 腎功能指標 54
5.5. SWE對於第二型糖尿病大鼠肝臟脂質含量之影響 54
5.5.1. 肝臟所含之TG及TC 54
5.5.2. SWE對於第二型糖尿病大鼠肝臟切片之影響 55
5.5.3. SWE調控第二型糖尿病大鼠肝臟脂肪酸代謝相關蛋白 55
5.6. SWE具有保護第二型糖尿病大鼠之腎臟的作用 57
5.6.1. 於HE stain切片觀察腎絲球萎縮以及腎間質表現量 57
5.6.2. 於PAS切片觀察醣類堆積情形 58
5.6.3. 於Masson氏三色染色法觀察膠原蛋白增生情形 58
六、討論 59
七、實驗結果圖表 63
八、參考文獻 78

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