骨桥蛋白在胆固醇结石患者胆汁中的表达及成核作用研究

The expression of osteopontin and its nucleating role in gallbladder bile of patients with cholesterol gall- stone

目的探讨骨桥蛋白在人胆固醇结石形成中的作用。方法36例胆固醇结石患者为结石组，19例肝移植供体为正常组，分别测定骨桥蛋白、钙离子及脂质成分在胆囊胆汁中的含量，用成核时间法研究骨桥蛋白在胆汁中的成核作用。结果骨桥蛋白呈剂量依赖性地抑制胆固醇自发成核。50yg／ml的骨桥蛋白可分别使结石组和正常组胆汁的成核时间延缓48．90％和17．07％，100pLg／ml的骨桥蛋白可使成核时间延缓91．51％和32．93％；并可抑制钙离子诱导的促成核作用。50tLg／ml骨桥蛋白＋钙离子可分别使结石组和正常组胆汁成核时间延缓75．78％和33．96％，而100ug／ml骨桥蛋白＋钙离子则使成核时间分别延缓125．90％和62．26％。结石组胆汁中胆固醇、磷脂、胆汁酸及胆固醇饱和指数均显著高于正常组胆汁（P〈0．05），而骨桥蛋白和钙离子含量则明显低于正常组胆汁中的含量（P〈0．05）。结论骨桥蛋白可抑制胆固醇成核，并参与胆结石的发生发展。

Objective To investigate the role of osteopontin （OPN） in cholesterol gallstone formation. Methods Gallbladder bile was obtained from patients with cholelithiasis （n=36, the experi mental group） and from donors of liver transplantation （n=19, the control group）. OPN, calcium ion and lipid were analysed quantitively. The nucleating role of OPN in bile was evaluated using nucleating time （NT） approach. Results OPN inhibited cholesterol nucleation in a dose dependent manner. OPN （50 ug/ml and 100ug/ml） prolonged NT by 48.90%（91.51%） and 17.07% （32.93%） in lithogenic and control bile, respectively. OPN （100ug/ml） also inhibited the nucleating effect induced by calcium ion. Furthermore, a combination of OPN （50ug/ml） and calcium prolonged NT by 75. 78% and 33.96% in lithogenic and control bile, respectively. A combination of OPN （100 ug/ml） and calcium prolonged NT by 125.9% and 62.26% in the 2 groups. The contents of osteopontin and calcium were significantly lower in lithogenic bile than control bile （P〈0.05）. On the other hand, the cholesterol saturation index and the contents of cholesterol, phospholipid and bile acid were significantly higher （P（0.05）. Conclusions OPN inhibited cholesterol gallstone formation. It may be involved in the pathogenesis of cholelithiasis.