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多価不飽和脂肪酸によるマイクロドメイン形成と消化管薬物吸収促進作用との関連性

多不饱和脂肪酸形成微结构域与胃肠道药物吸收促进作用的关系

基本信息

批准号：
17790133
负责人：
大貫義則
金额：
$ 1.09万
依托单位：
Hoshi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

様々な生理活性作用が知られる多価不飽和脂肪酸を食品や製剤添加物として消化管に適用すると、細胞膜マイクロドメインの形成変化が起こり、それによって薬物吸収性などの膜機能が変化するとの仮説を立て、モデル膜や培養細胞を用いた検討を行った。まず、組成の異なるモデル膜に各種脂肪酸を適用し、界面活性剤不溶性膜画分量や蛍光異方性などの測定を行った。その結果、ドコサヘキサエン酸(DHA)やエイコサペンタエン酸(EPA)の多価不飽和脂肪酸は、コレステロールを含まない膜に対しては非常に強力な膜流動化作用を示すものの、コレステロールを含む膜に対しては、その作用が著しく減弱することが明らかになった。さらに、オレイン酸のような不飽和脂肪酸と作用を比較したところ、両者の膜への作用様式は異なっていた。以上の結果から、多価不飽和脂肪酸がマイクロドメインの形成を促進させる可能性を見出した。すなわち、多価不飽和脂肪酸はコレステロールが豊富に含まれる膜領域(マイクロドメイン)には作用せず、膜に対して不均一に作用するため、結果として流動性の高い膜領域と低い膜領域の相分離を助長して、マイクロドメインの形成を促進する可能性が考えられる。続いて、この考察をもとに培養細胞(Caco-2)を用いて検討を行った。検討として、多価不飽和脂肪酸を適用した細胞から、界面活性剤不溶性膜画分と可溶性膜画分を分画し、それぞれのフラクションに含まれる膜タンパク量を評価した。なお、本研究では対象とする膜タンパクに、マイクロドメインへの分布が報告されているP糖タンパク(P-gp)を選択した。その結果、多価不飽和脂肪酸を適用しても、各フラクションのP-gp量に目立った変化は認められなかった。したがって、現在までのところ、モデル膜での結果を支持するような結果は得られていない。今後は条件を変えてさらに検討を進める予定である。

The effects of physiological activity are known to be sensitive to the effects of dietary and fatty acids, food additives, digestive tract cancer, cell membrane formation and absorption. The membrane machine can be used in the culture of the digestive tract and the cells of the digestive tract. The components of various fatty acids, such as fatty acids, insoluble films, and so on, were determined by optical spectroscopy. The results show that the membrane flow is very strong. The results show that the membrane flow is very strong. The results show that the membrane has a strong effect on the flow of the membrane. the results show that there is a strong effect on the flow of the membrane. the results show that there is a strong effect on the flow of the membrane. the results show that there is a strong effect on the flow of the membrane. the results show that there is a strong effect on the flow of the membrane. The effects of fatty acids and fatty acids are better than those of fatty acids, and the effects of fatty acids are better than those of fatty acids. The above results show that the formation of polyphenols, polyphenols and fatty acids can promote the formation of fatty acids. The concentration of polyphenols, polyphenols and fatty acids is very high in the field of membrane, the effect of membrane is different, the effect of membrane is not uniform, and the results show that it is possible to promote the formation of phase separation in the field of high-temperature membrane and low-temperature membrane. Please make a survey of the cell (Caco-2) in order to make sure that you do not know what to do. Insoluble film, soluble film, fatty acid, fatty acid and fatty acid. The results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study The results, polyphenols and fatty acids were measured by P-gp. The results show that the results are supported and the results show that the results are not correct. In the future, the terms and conditions will be improved.