探討大豆異黃酮素、維生素 E 及維生素 D 對去除卵巢大鼠之肥胖與生理活性之影響

Study on the efficacy of soy-isoflavones, vitamin E and vitamin D on obesity and biological activities in ovariectomized rats

洪玉軒(Yu-Hsuan Hung)

指導教授 ： 張基隆

高雄醫學大學/醫學院/生物化學研究所/碩士(2007年)

摘要

更年期後婦女因雌激素的缺乏，易導致肥胖、冠狀心臟疾病及代謝失調症候群發生。本實驗以大鼠切除卵巢 (ovariectomizy，OVX) 的方式，模擬女性停經後之生理狀況，探討大豆異黃酮素、維生素 E 及維生素 D 對去除卵巢大鼠在代謝系統與體內脂肪體積之生理活性的影響。實驗設計方面，將12週大的大鼠隨機分成以下8個組別：(1) Sham-operated(Sham，偽手術而不去除卵巢) (2) OVX (3) OVX 投予 17β- estradiol (4) OVX 投予 soy extracts (含isoflavones ) (5) OVX 投予維生素E (6) OVX 投予 soy extract 添加維生素E (7) OVX 投予維生素D (8) OVX 投予 soy extract 添加維生素D，每組8隻，總共餵食40週，實驗結束後測定血清中glucose、triacylglycerol 和 cholesterol 的含量。再以 RT-PCR 及 Quantitative real-time PCR 技術探討大鼠肝臟與脂肪組織內脂肪酸代謝相關分子標幟及下視丘內調控食慾行為之基因表現的變化量及利用雙能量 X 光測定儀 (DEXA) 測定大鼠體組成的變化。結果顯示，OVX 組投予大豆異黃酮素或併用維生素 E 或維生素 D，在體重的控制方面與 OVX 控制組有顯著的差異，能避免因雌激素的缺乏而造成體重快速的增加，類似於直接給予雌激素的效果。在血清測定方面，投予大豆異黃酮素或併用維生素 E 或維生素 D，能降低血液中 triacylglycerol 和 cholesterol 的含量，避免因 OVX 造成血脂肪上升的情形。在體組成方面，投予大豆異黃酮素或併用維生素 D 或維生素 E 後，能有效降低大鼠體內腹腔及骨盆區內脂肪組織含量，避免因 OVX 造成該二區脂肪累積的情形。在組織萃取 mRNA 方面，投予大豆異黃酮素或併用維生素E 或維生素 D 後，可以調控代謝脂肪酸的相關基因 leptin, lipoprotein lipase (LPL) 及 peroxisome proliferator-activated receptor γ (PPARγ) 的表現，避免因 OVX 造成體內代謝失調，而有脂肪肝與脂肪酸累積在脂肪組織內的情形；同時，也具有降低下視丘中 neuropeptide Y 的表現，以降低食慾的產生。依現階段的研究結果初步證實，異黃酮素具有調節體內能量代謝平衡的效果，可能是藉由降低食慾的產生，與抑制脂肪酸在肝臟與脂肪組織內累積，並活化脂肪相關代謝分子來加速代謝的平衡；而維生素 D 或維生E 本身或添加於異黃酮素並未能具此效力。

關鍵字

肥胖 ； 異黃酮素 ； 更年期 ； 脂質代謝

並列摘要

Body fat accumulation, coronary heart disease and metabolic syndrome are often associated with estrogen decline in menopause. This study aimed to determine the efficacy of soy isoflavones, Vitamin E and Vitamin D on body fat content and its related metabolic parameters in ovariectomized (OVX) rats which mimic women in menopause. Twelve-weeks old female rats were randomly assigned to eight groups: (1) Sham-operated (sham) (2) OVX (3) OVX treated with 17β-estradiol (4) OVX treated with soy extract (5) VX treated with Vitamin E (6) OVX treated with soy extract and Vitamin E (7) OVX treated with Vitamin D3 (8) OVX treated with soy extract and Vitamin D3 and lasted for 10 months. After treatment, serum contents of glucose、triacylglycerol and cholesterol were detected. In addition, RT-PCR and Quantitative real-time PCR was used to find out the changes of fatty acid metabolism related molecular markers in liver and adipose tissue, meanwhile, the gene which regulates appetite in hypothalamic was assayed. Furthermore, the weight change was recorded and body fat content was detected by Dual Energy X-ray Absorptiometry (DEXA). Results showed that OVX caused marked increase in body weight due to increase in body fat contents. In accordance with this, serum cholesterol and triacylglycerol (TG) were enhanced. All these increases could be significantly reduced by treatment of soy extract alone or in combination with Vitamin E or Vitamin D. Genes expressions of fatty acid metabolism and appetite, such as leptin, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ) and neuropeptide Y were affected by OVX, but these were reversed by treatment of soy extract alone or in combination with Vitamin E or Vitamin D groups. Our results suggest soy isoflavones indeed have effects on regulating energy metabolism by affecting some gene expressions to decrease appetite and suppress fatty acid accumulation, whereas vitamin E or vitamin D has no effects on these.

並列關鍵字

Obesity ； Isoflavone ； Menopause ； Lipid metabolism

參考文獻

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