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  • 學位論文

化學修飾之大豆異黃酮延緩卵巢摘除小鼠之骨質疏鬆的功效

Anti-osteoporotic Effects of Modified Genistein in Ovariectomized Mice

指導教授 : 謝淑貞
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摘要


國內外很高比例的停經後婦女都患有骨質疏鬆症,帶來很多危害健康的風險,例如骨折的產生。其主要病因為雌激素缺乏。臨床上常用的賀爾蒙治療法即是給予雌激素,可減少骨折風險但是卻會引起不良副作用,例如增加罹患乳癌與心血管疾病的風險。大豆異黃酮(genistein)是一種植物性雌激素,因其結構與人體雌激素類似,可與體內雌激素受體結合並有類雌激素的效果。已有研究顯示genistein可用於減緩部分女性更年期症狀,且對於骨質疏鬆的延緩甚至預防較賀爾蒙給予有效用佳卻幾乎沒有副作用的優勢。但是身為親油性的物質,它的水溶性並不好。為了提升生物利用率,我們藉由化學修飾改變其結構與增加其水溶性,也在體外試驗看到更佳的吸收率。因此本研究利用停經後骨質疏鬆的小鼠模式探討genistein與modified genistein (genistein 7-O-phosphate)兩者保護骨頭的作用。研究結果顯示modified genistein比genistein更能維持骨頭微結構的完整,因此推測modified genistein具有更佳的抗骨鬆效用。

並列摘要


Increase in bone turnover associated with ovarian hormone deficiency after menopause facilitates the development of postmenopausal osteoporosis. Conventional treatment for postmenopausal osteoporosis is hormone replacement therapy (HRT) which is a prescription of exogenous estrogen. However, several undesirable side effects are associated with HRT, including elevated risk of breast cancer and cardiovascular events. On the other hand, genistein is an estrogenic isoflavone found mainly in soybeans and soy products; long-term clinical studies indicate that genistein appears to be one of the most effective and safe isoflavone in preserving bone health. Nevertheless, its poor aqueous solubility contributes to low bioavailability. An isoflavone derivative, genistein 7-O-phosphate, has been obtained by microbial bioconversion and found to be more rapidly absorbed into the intestine than the parent drug in Caco-2 absorption study. Evaluation of micro-computed tomography analysis of bone microarchitecture shows that treatment with genistein 7-O-phosphate results in more complete preservation of bone tissue integrity than genistein. Given this finding, the modified genistein seems to have greater potential in preserving bone health than genistein.

參考文獻


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