建立評估保健食品改善代謝症候群功效之動物模式

To Develop an Animal Model for Evaluating the Effect of Functional Food on Metabolic Syndrome Study

廖偉翔(WEI-HSIANG LIAO)

指導教授 ： 蔡敬民

中原大學/理學院/化學研究所/碩士(2009年)

https://doi.org/10.6840/cycu200900211

摘要

論文題目：建立評估保健食品改善代謝症候群功效之動物模式
研究生：廖偉翔
指導教授：蔡敬民 博士
摘要
人們有代謝症候群這種概念已經將近80年，它曾被稱為代謝症候群X或胰島素阻抗症候群，是一種日見普遍因腹部肥胖而造成代謝紊亂的疾病。代謝症候群有5個主要指標，包括腹部肥胖、高血糖、血壓、三酸甘油酯和低的高密度脂蛋白膽固醇 (HDL-C) 。本研究的目的是要建立一個可以評估機能性食品對改善或預防代謝症候群的倉鼠模式
實驗I
本實驗旨在建立能引發倉鼠具「高血脂」與「高血糖」，甚或有「高體脂肪」的代謝症候群動物實驗模式。50隻8週大倉鼠，逢機均分為5組，分別餵食AIN93G的飼料或經修飾的12%高油脂低蔗糖 (HOLS) 、高油極高蔗糖 (HOVHS) 或攝取HOLS、HOVHS飼料並同時施打30 mg/d nicotinamide (NA) ＋10 mg/d Strepozotocin (STZ) (HOLS+、HOVHS+) 。每週測量體重，每2星期從眼窩取得血液樣本，測空腹血漿血糖、三酸甘油酯 (TG) 、膽固醇 (TC) 和HDL-C；每4週做一次口服葡萄糖耐受性試驗 (Oral Glucose Tolerance Test, OGTT) ，餵食12週後將所有倉鼠犧牲分析。結果顯示單以蔗糖作為CHO來源加上12%高油脂之飼料在12週內並未能有效明顯誘發高血糖，且原以『空腹血糖值』作為判斷是否已誘發高血糖之指標，然雖動物已誘發高血糖，卻因12小時之空腹會令血糖值又回到基礎線值，因此發現並不宜以『空腹血糖值』來作為判斷是否已誘發高血糖之指標，而應以OGTT來判斷，且12週長期施打低劑量STZ應該沒有必要，應可縮短。
實驗II
本實驗嘗試使用極高油脂與添加果糖來誘發高血糖與高血脂。20隻8週齡倉鼠，逢機分成4組，分別餵食修飾為22%的極高油脂27.95%高蔗糖20%高果糖 (VHOHF) 、極高油脂7.95%低蔗糖40%極高果糖 (VHOVHF) 飼料配方或同時每天施打30 mg/d NA+10 mg/d STZ (VHOHF+、VHOVHF+) 4週。每週測量體重，每2星期測空腹血漿血糖、TG、TC和HDL-C，每4週做一次OGTT，餵食14週後將所有倉鼠犧牲，加以分析。實驗結果顯示沒施打STZ的二組血糖與部分血脂指標改變仍不是很明顯，有施打STZ組較理想，尤其VHOHF+，但似乎STZ可不必那麼多。
實驗III
根據實驗I與II的實驗結果，修訂成實驗III的誘發方法，其結果顯示讓倉鼠先攝取2週的極高油脂 (22%) 高蔗糖 (27.95%) 高果糖 (20%) 之誘發飼料，然後開始施打30 mg NA + 10 mg STZ，前2週每天施打1次，後2週每2天施打1次，然後停止施打藥劑，僅攝取誘發飼料4週，讓動物慢慢誘發出胰島素阻抗現象與高血脂等代謝症候群，如此前後共10週的處理應是一誘發倉鼠產生代謝症候群可行之模式。已誘發代謝症候群的倉鼠即可逢機分配到檢測保健食品是否能改善代謝症候群的實驗組之中進行評估實驗。本實驗嘗試檢測4項不同之改善代謝症候群複方，實驗結果有些較如預期有改善代謝症候群的效果；但有些並未出現預期應有之效果，其問題出在何處？尚待進一步探討。

關鍵字

代謝症候群 ； 肥胖 ； 糖尿病 ； 胰島素阻抗

並列摘要

Title: To develop an animal model for evaluating the effect of functional food on metabolic syndrome study
Graduate Student: Weihsiang Liao
Advisor: Dr. Jimmy Tsai

Abstract
The concept of the metabolic syndrome has existed for at least 80 years. The metabolic syndrome (MS) which was called syndrome X or insulin resistance syndrome is a common metabolic disorder that results from the increasing prevalence of abdominal obeses. The 5 parameters of MS include abdominal obesity, high blood glucose, pressure, triacylglycerol (TG) and low HDL-C. The purpose of this study was to establish a hamster research model that can evaluate the effect of a functional food on improving or preventing MS.
Trial I：
The study wanted to induce high blood lipid, glucose and even high body fat in a hamster for MS studies. Fifty 8 weeks old male Syrian Golden hamsters were randomly assigned into 5 groups, 10 each. Each group was treated AIN93G diet or a modified diet that contained 12% high oil with low sucrose (HOLS), high sucrose (HOVHS), or HOLS or HOVHS diet plus 30 mg/d nicotinamide (NA) + 10 mg/d Strepozotocin (STZ) injections (HOLS+, HOVHS+). Measured body weights every week and took blood samples from ocular fossa every 2 weeks. Fasting plasma glucose, TG, TC and HDL-C were measured. Oral glucose tolerance tests (OGTT) were operated every 4 weeks. After 12 weeks feeding, all hamsters were sacrificed under isoflurane anesthesia for further analyses. The results demonstrated that using sucrose as only CHO source plus 12% high oil diet couldn’t induce high blood sugar in 12 weeks. In the study, level of fasting blood glucose was a major indicator to distinguish whether a high blood glucose has been induced. It was found that the level of fasting blood glucose was not a good indicator, should use OGTT, and STZ shouldn’t be given for 12 weeks.
Trial II：
Super high fat and fructose diets were tested in the study. Twenty 8 weeks old male Syrian Golden hamsters were randomly assigned into 4 groups, 5 each. Each group was fed 22% very high oil with 20% high fructose high sucrose (VHOHF), 40% very high fructose high sucrose (VHOHF), or VHOHF or VHOVHF diet plus 30mg/d NA + 10mg/d STZ injections (VHOHF+, VHOVHF+) for 4 weeks. All the measures were same as the ones in Experiment I. Results showed that blood sugar and part of blood lipid parameters were not change significantly in without STZ groups, whereas the STZ groups were better, especially VHOHF+. But, it seems dose of STZ can be reduced.

Trial III：
According to the results from experiments I and II, treatments were further slightly modified in the study. The results showed that hamsters were successfully induced insulin resistance slowly with high blood lipid for MS study by continuously taking a 22% very high oil diet with 20% fructose and 27.95% sucrose for whole inducing period, but after 2 weeks feeding, 30 mg NA + 10 mg STZ was given every day for 2 weeks and every 2 days for 2 weeks, and then only inducing diet for another 4 weeks. After MS induction, 40 hamsters were randomly assigned into 4 experimental groups to evaluate the effects of our 4 various MS combination formula. The results demonstrated that some formula had nice improvements on MS, however, some were not. It might need further studies on MS formula.

並列關鍵字

Metabolic syndrome ； obesity ； diabetes ； insulin resistance

參考文獻

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22. 行政院衛生署國民健康局 2006 公告修訂代謝症候指標.

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