权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of cholesterol crystallization-promoting protein in the pathogenesis of cholesterol gallstone.

胆固醇结晶促进蛋白在胆固醇胆结石发病机制中的作用。

基本信息

批准号：
05670445
负责人：
TANAKA Naomi
金额：
$ 1.34万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Rapid cholesterol crystallization in bile is the critical event leading to cholesterol gallstone formation. Several glycoprotein promoters (immunoglobulins, phospholipase C,aminopeptidase N) of cholesterol crystallization have recently been reported in bile with gallstones, which have received world-wide attention. We have successfully isolated a new promoter and identified it as alpha_1-acid glycoprotein. However, no study compared these promoters in vitro and their precise role in the pathogenesis of gallstones remains unknown. Therefore, we aimed in this study to clarify the role of these cholesterol crystallization-promoters in the pathogenesis of gallstones. Firstly, the cholesterol crystallization-promoting activity of these glycoproteins was compared in vitro. It was found that only alpha_1-acid glycoprotein and immunoglobulins exsert the promoting activity at their physiologic levels in bile. Secondly, the biliary levels of alpha_1-acid glycoprotein in various gallstone and non-gallstone patients were assayd by a newly established specific ELISA and compared with the cholesterol nucleation time in bile. This revealed that the alpha_1-acid glycoprotein level is not altered in biles with solitary cholesterol or pigment gallstones but it is specifically elevated in biles with multiple cholesterol gallstones and that its increase is associated with rapid nucleation time. The potent promoting activity in vitro as well as the specific increase in bile (in vivo) with multiple cholesterol gallstones suggest the critical role of the biliary alpha_1-acid glycoprotein in the formation of multiple cholesterol gallstones.

胆汁中胆固醇的快速结晶是导致胆固醇结石形成的关键事件。近年来，在胆结石患者的胆汁中发现了几种促进胆固醇结晶的糖蛋白促进剂(免疫球蛋白、磷脂酶C、氨基肽酶N)，引起了世界各国的广泛关注。我们成功地分离到一个新的启动子，并将其鉴定为α_1-酸性糖蛋白。然而，没有研究在体外比较这些启动子，它们在胆结石发病机制中的确切作用仍不清楚。因此，我们在这项研究中旨在阐明这些胆固醇结晶促进剂在胆结石发病机制中的作用。首先，比较了这些糖蛋白的体外促胆固醇结晶活性。在胆汁中，只有α_1-酸性糖蛋白和免疫球蛋白在其生理水平上表现出促进活性。其次，用新建立的特异性酶联免疫吸附试验检测了不同胆结石和非胆结石患者胆汁中α_1-酸性糖蛋白的水平，并与胆汁中胆固醇成核时间进行了比较。这表明α_1-酸性糖蛋白水平在单纯胆固醇结石或色素结石的BILs中没有改变，但在多发胆固醇结石的BILS中显著升高，其增加与快速成核时间有关。胆汁α1-酸性糖蛋白在多发性胆固醇结石的形成过程中，在体外具有很强的促进活性，体内胆汁中的特异性增加，提示胆汁α1-酸性糖蛋白在多发性胆固醇结石的形成中起关键作用。