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  • 學位論文

以高果糖模式探討紅麴 Monascus purpureus CWT715 發酵液對胰島素阻抗之改善作用及抗氧化作用

Effects of Monascus purpureus CWT 715 on Insulin Resistance Prevention and Antioxidative Properties in Fructose - fed Rats

指導教授 : 黃晉修 張駿志
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摘要


代謝症候群是現代社會相當重視的議題,症狀包括有高血壓、高胰島素血症、胰島素阻抗以及高三酸甘油酯等。一旦胰島素阻抗繼續惡化則可能會導致第二型糖尿病。許多研究證實,攝取適量抗氧化物質有助於代謝症候群之預防。紅麴具有良好的抗氧化特性,同時其二級代謝產物具有降血壓、血脂以及血糖之作用,但對於第二型糖尿病是否有預防的作用仍待釐清。 研究以高果糖為模式,探討紅麴預防胰島素阻抗以及抗氧化之作用。試驗前分析紅麴中總酚含量,發現於發酵第三天之總酚含量最高,因此選用第三天紅麴粉末做為管餵之樣品。將SD大鼠分成五組,每組各8隻:包括 (1) 控制組,給予標準飼料;(2) 高劑量紅麴組,給予標準飼料並管餵高劑量紅麴 (200 mg/kg BW-2d);(3) 高果糖組,給予高果糖飼料;(4) 高果糖低劑量紅麴組,除高果糖飼料並管餵低劑量紅麴 (50 mg/kg BW-2d);(5) 高果糖高劑量紅麴組,高果糖飼料並管餵高劑量紅麴。分析項目包括禁食血糖、胰島素、總膽固醇、三酸甘油酯、抗氧化指標 (SOD、GPx、catalase、GSH)。 分析不同發酵天數紅麴的總酚,發現第三天條件之總酚含量較高,約為299 μg/ mL,推測總酚含量應與其抗氧化作用有關。經二十週試驗後發現,與控制組相比高果糖組有胰島素阻抗之現象,包括體重增加3%、血糖略為上升、胰島素含量增加63% (P<0.05),而肝臟脂肪三酸甘油酯 (triglyceride, TG)、總膽固醇 (total cholesterol, TC) 和非酯化脂肪酸 (non-esterified fatty acid, NEFA) 也分別上升45%、33%和18% (P<0.05)。與果糖組相比,同時管餵低與高劑量紅麴後,體重和血糖較果糖組低、胰島素含量分別降低84%和58%,而肝臟TC降低34%和27%、TG降低30%和21%以及NEFA降低30%和21% (P<0.05),皆趨近控制組,且在肝臟組織切片中脂肪空洞也較小,有減緩脂肪肝形成之趨勢。抗氧化方面,果糖組肝臟DNA損傷增加約20%,且血清中GPx和GSH皆顯著較控制組低 (P<0.05)。同時管餵低高劑量紅麴後,可降低DNA損傷達51%,抗氧化酵素SOD、GPx、CAT與GSH亦有上升的趨勢,分別上升36%、40%、18%與12%,且多呈劑量關係。。 本試驗證實,給予高果糖後會誘導大鼠產生胰島素阻抗的現象並增加氧化傷害,而經給予紅麴後可減輕胰島素組抗以及脂肪肝的形成,並降低高果糖所造成的氧化壓力。因此,紅麴對於預防第二型糖尿病應有不錯的潛力。

並列摘要


Metabolic syndrome is a cluster of disorders, including hypertension, hyerinsulinemia, insulin resistance and hypertriglyceridemia that increase for type 2 diabetes. Natural antioxidants were reported to ameliorate metabolic syndrome. Studies have suggested that Monusus exerts antioxidative function and decreases plasma glucose and lipid. These function may related with its secondary metabolites such as pigments, monacolins, -aminobutyric acid (GABA), dimerumic acid and flavonids are produced. Thus, it seems that M. purpureus may reduce diabetic complications. However, the effect and mechanism of M. purpureus CWT715 on insulin resistance, which is widely associated with cardiovascular complications, is still unknown. There is analysis of total phenol content of M. purpureus CWT715, The highest total phenol production (299 μg/ mL) was found when third day. Male Sprague – Dawley rats were randomly assigned into five experimented groups: including group control , fed with standard chow diet; group HM, fed with standard chow diet and plus high dose Monascus 200 mg/ kg BW per 2 days by gavage; group HF, fed with high fructose diet alone; group HFLM, fed with high fructose diet plus Monascus 50 mg/ kg BW per 2 days by gavage; group HFHM, fed with high fructose diet plus Monascus 200 mg/ kg BW per 2 days. Analysis included fasting blood glucose, insulin, total cholesterol, triglyceride, antioxidant index (SOD, GPx, catalase, GSH), Result of our study showed that the rats exhibited significantly plasma insulin and triglyceride levels with fructose-fed. This study would examine somatic index (AST and ALT level in serum) and liver biopsy. In these results, AST and ALT level in serum by Monascus experimental group were not significantly increased, there was exhanced the level of fatty liver and reduced the fatty liver between Monascus experimental group and control group. In antioxidative capacity analyses, HFLM significantly increased SOD, catalase and GSH in plasma enzyme activity; and HFHM is also increased SOD 36%, GPx 40%, catalase 18% and GSH 9% (p<0.05). In conclusion, Monascus may have beneficial effects to reduced the concentration of insulin, TG, TC increased, and hence decrease the risk of oxidative stress

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