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Experimental analysis of inhibitory effect of n-3 polyunsaturated fatty acid on cholesterol gallstone.

n-3多不饱和脂肪酸对胆固醇胆结石抑制作用的实验分析。

基本信息

批准号：
08670553
负责人：
ABEI Masato
金额：
$ 1.41万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670553/
关键词：
cholesterol gallstone eicosapentaenoic acid fish oil n-3 polyunsaturated fatty acids phospholipids lecithin mucin

项目摘要

The incidence of cholesterol (CH) gallstone in Japan has dramatically increased in the past 50 years, during which intake of fish oil or n-3 polyunsaturated fatty acids (PUFA) has sharply declined. We aimed to clarify both in vivo and in vitro our hypothesis that eicosapentaenoic acid (EPA), a n-3 PUFA,might have a preventive effect on CH gallstone. The effect of EPA was compared with other fatty acids or bezafibrate in hamsters fed CH-rich diet. It was revealed that among various fatty acids only EPA inhibits the CH crystallization and gallstone formation in the hamster. This was accompanied by both increased total concentration and altered fatty acid composition (an increased EPA and decreased linoleic acid and arachidonic acid) of biliary phospholipids. How these changes in biliary lipids relate to the preventive effects was further studied in vitro. In the model bile system, increases in phosphatidylcholine (PC) that contains either EPA (16 : 0-20 : 5 PC), linoleic acid (16 : 0-18 : 2 PC), or arachidonic acid (16 : 0-20 : 4 PC) all decreased the vesicular CH saturation and similarly exerted potent and dose-dependent inhibitory effect on CH crystallization. These effects were clearly stronger than bile acids. Finally, in a culture system of gallbladder epithelia, EPA significantly inhibited the arachidonic acid-induced mucus glycoprotein secretion. The dual inhibitory effects of EPA on the two key pathogenetic factors (CH crystallization and mucus glycoprotein secretion) suggest critical roles of the n-3 PUFA in the formation and prevention of CH gallstone disease.

在过去的50年里，日本胆固醇（CH）胆结石的发病率急剧上升，而在此期间，鱼油或n-3多不饱和脂肪酸（PUFA）的摄入量急剧下降。我们的目的是在体内和体外澄清我们的假设，即二十碳五烯酸（EPA），一种n-3 PUFA，可能对CH胆结石有预防作用。比较了EPA与其他脂肪酸或苯扎贝特对富含ch的仓鼠的影响。结果表明，在多种脂肪酸中，只有EPA能抑制仓鼠胆石的形成和CH的结晶。这伴随着胆磷脂总浓度的增加和脂肪酸组成的改变（EPA增加，亚油酸和花生四烯酸减少）。在体外进一步研究了这些胆道脂质的变化与预防作用的关系。在模型胆汁系统中，含有EPA （16:0 - 20:5 PC）、亚油酸（16:0 - 18:2 PC）或花生四烯酸（16:0 - 20:4 PC）的磷脂酰胆碱（PC）的增加都降低了囊泡CH饱和度，并同样对CH结晶发挥了有效的剂量依赖性抑制作用。这些作用明显强于胆汁酸。最后，在胆囊上皮培养系统中，EPA显著抑制花生四烯酸诱导的粘液糖蛋白分泌。EPA对两种关键致病因子（CH结晶和粘液糖蛋白分泌）的双重抑制作用提示n-3 PUFA在CH胆石病的形成和预防中起关键作用。