臺灣博碩士論文加值系統

絕育手術可能會引起正常的大鼠體重增加，活動減少，身體脂肪含量的增加，從而增加了患有糖尿病的風險。雌激素(Estradiol)被認為可以調控脂質的代謝和糖類的穩態，同時對於攝食行為和能量平衡有著重要作用。相似的是，三價格( Trivalent Chromium)，同樣被認為對糖類，脂質的代謝有著重要調控作用。因此，本研究的目的是比較單獨使用和合用雌激素與三價格，並觀察其對於絕育後大鼠脂質含量和血糖的調控影響。本實驗採用10週齡的雌性大鼠，進行卵巢子宮摘除術後，平均分為五個小組，每組6只，並控制每組大鼠的平均體重在250g左右。飼養3週後，測量體重，收集血液用以測量血糖、胰島素、甘油三酯及膽固醇含量。隨後按照分組給藥，分別為單獨鉻離子組(Cr group), 低劑量雌激素組(low-dose E2 group), 低劑量雌激素加鉻組(low-dose E2 with Cr group), 高劑量雌激素組(high-dose E2), 高劑量雌激素加鉻組(high-dose E2 with Cr group)。其中三價格的劑量為80 μg/kg，低劑量雌激素劑量為0.025 mg/kg，高劑量雌激素劑量為0.5mg/kg。所有藥物均以口服給予，每天一次，持續12週。每週測量一次體重，並分別在16、19、22、25週採血用以測量血糖、胰島素、甘油三酯和膽固醇。在實驗的最後，對所有大鼠進行腹腔注射葡萄糖耐受性試驗(IPGTT)。結果顯示，十二週中，低劑量雌激素，低劑量雌激素加鉻以及單獨鉻三組大鼠體重增長率及體重無顯著差異，高劑量雌激素組體重增長率自14週開始顯著低於單獨鉻(P<0.05)，高劑量雌激素加鉻組14-19週中體重增長率顯著低於單獨鉻，但兩組之間無顯著差異。給藥12週後，單獨鉻組大鼠膽固醇和甘油三酯都上升。低劑量雌激素加鉻對膽固醇的降低效果較低劑量雌激素好，但差異不顯著；高劑量雌激素組效果較高劑量雌激素加鉻組好，差異同樣不顯著。對於甘油三酯的降低效果，低劑量雌激素和低劑量雌激素加鉻兩組給藥12週後，降低顯著，高劑量雌激素兩組則降低不顯著。但兩大組內小組間均沒有顯著差異。低劑量加鉻組在13-22週內，有較低的胰島素抵抗，相較於低劑量雌激素組，但在長期給予中，單獨低劑量雌激素擁有較低的胰島素抵抗和較高的胰島素敏感性。在13-19週內高劑量雌激素加鉻組和單獨鉻組，擁有較低的胰島素抵抗，且胰島素敏感性顯著高於單獨高劑量雌激素組。在葡萄糖耐受性試驗中，低劑量雌激素組、低劑量雌激素加鉻組和單獨鉻組，三組大鼠葡萄糖及胰島素曲線下面積均無顯著差異；高劑量雌激素加鉻組大鼠葡萄糖曲線下面積顯著高於單獨鉻組和低劑量雌激素加鉻組，胰島素曲線下面積則顯著低於單獨鉻組。顯示了高劑量雌激素在長期給予中可能會造成胰島素分泌不足和糖耐量下降；低劑量雌激素在長期給予中可能會造成胰島素抵抗上升和敏感性下降。綜合以上的結果，本研究顯示了在絕育後的大鼠，聯合使用低劑量雌激素與三價鉻離子對膽固醇和甘油三酯具有良好的降低效果。同時在短期內，雌激素和三價鉻離子的結合治療可以緩解絕育對大鼠造成的胰島素抵抗，並增加胰島素的敏感性。

Neutering in normal rats may result in weight gain, decreasing activity levels, increasing lean and fat tissue compared with intact rats. Estradiol (E2) is considered widely as a regulator of lipid metabolism and glucose homeostasis, and plays a role in feeding and energy balance regulation. Similarly, trivalent chromium (Cr3+) is a trace element which involved in the metabolism of carbohydrates, lipid and proteins. Hence, the aim of this study is to figure out the effects of combination between E2 and Cr on lipid levels, as well as blood glucose level in ovariohysterectomized rats. For this purpose, we used 10-week-old female Sprague-Dawley rats to measure the body weight, blood glucose, plasma insulin, cholesterol, and triglyceride. At the end of the study, the intraperitoneal glucose tolerance tests (IPGTTs) were conducted. In this study, there was no significant difference among Cr, low-dose E2 treated group and low-dose E2 with Cr group in the terms of the body weight and the variant body weight ratio (VarBW%). The VarBW% of high-dose E2 group showed markedly lower than Cr group since 14th week, meanwhile, the high-dose E2 with Cr group showed notably lower than that in Cr group in the VarBW% values during 14th to 19th week (P<0.05). However, there was no significant difference between the values. Compared with before and after treatments, low-dose E2 with Cr group showed better effects on the decrease of cholesterol and triglyceride than low-dose E2 group, but no significant difference. There was no observable difference between high-dose E2 group and high-dose E2 with Cr group on the decrease of cholesterol and triglyceride. During 13th to 22nd week, low-dose E2 with Cr group had lower insulin resistance and higher insulin sensitivity than that in low-dose E2 group, although the situation was opposite at 25th week. Similarly, since 13th to 19th week, high-dose E2 with Cr group had lower insulin resistance and significantly higher insulin sensitivity than that in high-dose E2 group (P<0.05). In the IPGTTs, both glucose and insulin AUC0-90 of Cr group, low-dose E2 group and low-dose E2 with Cr group had no significant difference. The glucose AUC0-90 of high-dose E2 with Cr group was signally higher than Cr group and high-dose E2 group, but the insulin AUC0-90 was markedly lower than Cr group (P<0.05). According to all results, the combination of low dosage E2 and Cr showed the positive effects on the decrease of cholesterol and triglyceride. At the same time, during short-term treatments, the combination of E2 and Cr could remit insulin resistance induced by neutering, as well as the increase insulin sensitivity.

摘要 i
Abstract iii
Content v
List of tables vii
List of figures viii
Chapter 1 Introduction 1
1.1 Obesity and diabetes mellitus 1
1.1.1 Introduction of diabetes mellitus 1
1.1.2 Introduction of obesity 1
1.1.3 Introduction of cholesterol and triglyceride ..2
1.1.4 The effect of neutering on obesity and diabetes 2
1.2 Trivalent chromium 3
1.2.1 Introduction 3
1.2.2 The biological function of chromium 4
1.2.3 Chromium in obesity and lipid metabolism 4
1.2.4 Chromium in diabetes mellitus 5
1.3 Estrogen 6
1.3.1 Introduction of estrogen 6
1.3.2 The effect of estrogen in obesity 6
1.3.3 The effect of estrogen in diabetes mellitus 7
Chapter 2 Materials and methods 9
2.1 Animals 9
2.2 Experimental design 9
2.2.1 Ovariohysterectomy surgery (OHE) 10
2.2.2 Intraperitoneal glucose tolerance test (IPGTT) 10
2.3 Measurement of body weight and the variant body weight ratio% 10
2.4 Blood collection 11
2.5 Measurement of the concentration of glucose, insulin, triglyceride and cholesterol 11
2.5.1 Measurement of the concentration of glucose 11
2.5.2 Measurement of plasma insulin concentration 11
2.5.3 Measurement of triglyceride 12
2.5.4 Measurement of cholesterol 12
2.6 Homeostasis model assessment analysis (HOMA-IR) 13
2.7 QUICK analysis 13
2.8 Statistical analysis 13
Chapter 3 Results 14
3.1 The change of body weight and VarBW% 14
3.2 The concentration of plasma cholesterol 14
3.3 The concentration of plasma triglyceride 15
3.4 The concentration of blood glucose 16
3.5 The concentration of plasma insulin 16
3.6 The HOMA values 17
3.7 The QUICK value 17
3.8 The change of glucose and plasma insulin level during IPGTT. 17
Chapter 4 Discussion 43
4.1 The change of body weight 43
4.2 The concentration of cholesterol and triglyceride 44
4.3 The concentration of blood glucose and plasma insulin 45
4.4 The HOMA-IR and QUICK value 46
4.5 The change of blood glucose and plasma insulin level after IPGTTs 47
4.6 Conclusions 48
Reference 49

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