利用小鼠動物模式探討複方健康食品對代謝症候群危險因子之影響

當胰島素阻抗、肥胖、高血糖、血脂異常、高血壓等多項代謝症候群的危險因子綜合出現時，此個體將來罹患糖尿病和心血管疾病的風險也隨著增加。國人十大死因中與代謝症候群相關的疾病包括腦血管疾病、心臟疾病、糖尿病、腎病變和高血壓等，這些疾病都跟高血壓、高血脂和高血糖等代謝症候群的危險因子息息相關。因此為開發有效之複方健康食品以降低代謝症候群的危險因子，本研究以單套脂蛋白元E基因以及血栓素A2合成酶基因剔除小鼠，配合腹腔注射streptozotocin(STZ)及餵食高脂飼料來建立篩選有效複方健康食品之動物實驗平台，並進一步評估複方食材之效用。在餵飼一般飼料(空白組)、施打STZ且餵食高脂飼料(控制組)和施打STZ且餵食高脂飼料添加複方食材(實驗組)等餵飼18週的三組實驗中，顯示控制組小鼠，自第二週起其血漿葡萄糖和總膽固醇均顯著高於空白組，第八週後的口服葡萄糖耐受性試驗亦觀察到葡萄糖不耐症的現象。而犧牲後也發現控制組小鼠之血管內壁脂質堆積及肝臟三酸甘油酯和總膽固醇，皆高於空白組，而肝臟PPARα表達量則低於空白組，顯示長期餵食高脂飼料會造成其脂質代謝異常。而實驗組小鼠血漿葡萄糖、低密度脂蛋白膽固醇和總膽固醇皆與空白組相似，口服葡萄糖耐受性試驗亦未有胰島素阻抗現象發生，實驗組小鼠血管內壁脂質堆積以及肝臟中的PPARα表達、三酸甘油酯和膽固醇皆與空白組相似。因此總結本實驗結果，當單套脂蛋白元E基因以及血栓素A2合成酶剔除小鼠以STZ注射及高脂飼料餵食，可誘導出高血糖症、高膽固醇血症、高低密度脂蛋白膽固醇、降低肝臟PPARα表達、肝臟脂質代謝出現異常及血管內壁脂質堆積增加；而以添加複方食材的高脂飼料餵食可有效降低其高血糖、高膽固醇、高低密度脂蛋白膽固醇、並提升肝臟PPARα表達、改善肝臟對脂質的代謝異常及血管內壁脂質的堆積，本實驗結果發現複方食材可有效改善代謝症候群。

關鍵字

TXA2合成酶基因剔除小鼠；動脈粥狀硬化；血脂異常；高血糖症；脂蛋白元E缺陷小鼠；代謝症候群；健康食品

並列摘要

Metabolic syndrome is characterized by insulin resistance, obesity, hyperglycemia, lipid metabolic disturbance and hypertension as well as a cluster of other risk factors. When these risk factors are raised, the danger of diabetes and cardiovascular diseases also accompanies. In Taiwan, the top 10 deaths associated with metabolic syndrome are cerebrovascular disease, cardiovascular disease, diabetes mellitus, nephropathy and hypertension. In order to evaluate potential health foods that may ameliorate metabolic syndrome, a mouse model with the above risk factors must be created. In this thesis, mice with heterozygous apolipoprotein E (apoE) and heterozygous thromboxane A2 synthase gene were used. And experiment was performed by dividing the apoE+/-/TXAS+/- male mice into three groups: (1) blank group: mice were maintained on standard chow diet, (2) control group: mice were injected with streptozotocin (STZ) and fed with high fat diet, and (3) treatment group: mice were injected with STZ and fed with a mix of high fat diet and health food extracts. Our data shown that fasting plasma glucose and total cholesterol significantly increased in control group as compared to blank group started from the 2nd week. And glucose intolerance was demonstrated by OGTT in the 8th week. At the end of treatment, fasting plasma glucose, total cholesterol and triacylglyceride were significantly higher than blank group. Besides, in control group, both lipid accumulation in enface of aorta and liver triacylglyceride and total cholesterol were higher than the blank group. And the expression of PPARα in liver was lower than the blank group. It implies that long term high-fat diet feeding may induce lipid disturbance. In the same time, fasting plasma glucose, low density lipoprotein-cholesterol and total cholesterol in the treatment group were resembled to the blank group. Insulin resistance was not demonstrated in treatment group, too. Lipid accumulation in enface of aorta and PPARα expression, triacylglyceride as well as total cholesterol in the liver were also resembled to the blank group. Thus, in summary, mice injected with STZ and fed with high-fat diet for 18 weeks is a good model with hyperglycemia, hyperlipidemia, higher low density lipoprotein- cholesterol, decreased PPARα expression and disturbance of liver lipid metabolism in liver as well as increased lipid accumulation in enface of aorta. And the combination of four health foods can effectively ameliorate the disturbance of hyperglycemia, hyperlipidemia and low density lipoprotein-cholesterol, improve PPARα expression and lipid metabolism in liver, and reduce lipid accumulation in enface of aorta.

並列關鍵字

thromboxane A2 synthase gene knockout mice ； atherosclerosis ； lipid metabolic disturbance ； hyperglycemia ； Metabolic syndrome ； Potential health foods ； apolipoprotein E gene deficiency mice

參考文獻

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利用小鼠動物模式探討複方健康食品對代謝症候群危險因子之影響

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