A Study on the Pathogenesis of Cholesterol Gallstone Formation : Importance of Biliary Proteins and Biliary Lipid Particles.

为了评价胆汁蛋白和胆汁脂质颗粒在胆固醇结石形成机制中的作用，我们用透射电子显微镜进行了超微结构的研究。结论如下：1.人胆汁和过饱和模型胆汁溶液中存在三种不同类型的脂质颗粒，即卵磷脂-胆固醇小泡、胆盐胶束和盘状颗粒。载脂蛋白A-1是一种抗核因子，通过与盘状颗粒结合来稳定非胶束状脂肪颗粒，然后抑制向多层脂质体的转化。另一方面，肝脏将大量胆固醇排入胆汁，导致亚油酸和花生四烯酸大量并入胆脂酰卵磷脂，导致胆囊壁合成和分泌粘蛋白，这是一种原核因子。这是由花生四烯酸-前列腺素途径介导的。粘蛋白促进囊泡聚集和融合，导致快速成核。因此，胆固醇晶体成核受抗核因子和原核因子之间的平衡调节。此外，成核发生在非胶束状的脂质颗粒，即囊泡、盘状颗粒。

To evaluate the role of biliary proteins and biliary lipid particles in the pathogenesis of cholesterol gallstone formation, we performed an ultrastructural studies using transmission electron microscopy. Conclusions were as follow ;1. There are three different types of lipid particle in human gallbladder bile and supersaturated model bile solutions, lecithin-cholesterol vesicle, bile salt micelle, and discoidal particle.2. Apolipoprotein A-1, an anti-nucleating factor, stabilizes nonmicellar lipid particles by binding to discoidal particles, followed by inhibition of transformation to multilamellar liposome.3. On the other hand, a high hepatic output of cholesterol into bile correlates a high incorporaion of linoleate and arachidonate into biliarylecithin, resulting in the induced synthesis and secretion of mucin, a pronucleating factor, by the gallbladder. This is mediated by an arachidonate-prostanoid pathway. Mucin promotes vesicular aggregation and fusion, resulting in fastnucleation.Thus, cholesterol crystal nucleation is regulated by the balance between anti-nucleating factors and pronucleating factors. In addition, nucleation occurs from the non micellar lipid particles, i. e. vesicles, discoidal particles.