肝细胞低密度脂蛋白受体,胆汁中胆汁酸及胆固醇在兔胆囊结石过程中的动态变化

Study of bile acid, LDL receptor of hepatocytes during cholestrol gallstone formation in a rabbit model

目的 研究肝细胞低密度脂蛋白受体，胆汁中胆汁酸和胆固醇的动态变化及其在胆囊结石过程中可能的机制。方法 利用高胆固醇膳食（ｈｉｇｈ ｃｈｏｌｅｓｔｅｒｏｌｄｉｅｔ，ＨＣＤ） 诱发兔胆囊胆固醇结石模型，分别对进食高胆固醇膳食后１ 、２、３ 、４ 周组及对照组，采用双波长薄层扫描法测定胆汁中胆汁酸，硫磷铁法测定胆汁中胆固醇以及１２５ＩＬＤＬ放免标记法测定肝细胞低密度脂蛋白受体（ＬＤＬｒ）活性。结果 高胆固醇膳食后１ 周开始出现胆囊结石，２ 、３ 和４ 周组分别有４／１０，６／１０ 和７／１０ 例出现胆囊结石；胆汁中甘氨脱氧胆酸（ＧＤＣＡ） 和甘氨胆酸（ＧＣＡ） ，前者１ 周时明显升高，以后逐渐降低，但差异无显著性（ Ｐ＞０ ．０５），后者逐渐降低，以３ 和４ 周组明显（ Ｐ＜ ０．０５） ；胆汁胆固醇随着ＨＣＤ进食时间延长呈进行性升高，２ 、３ 、４ 周组与对照组比较差异有显著性（ Ｐ＜ ０ ．０５） ，３ 和４ 周组升高最明显，１２５ＩＬＤＬ 与ＬＤＬｒ 的最大结合力Ｂｍａｘ 在１ 周组略升高（ Ｐ＞ ０ ．０５） ，２ 周组逐渐下降，３ 和４ 周组时明显下降（Ｐ＜ ０．０５），解离常数（Ｋｄ） 值逐渐升高，以３ 和４ 周组明显（Ｐ＜ ０ ．０５） 。结?

Objective To study the mechanism of cholesterol gallstone formation.Method Rabbit models were induced by high cholesterol diet (HCD), bile acids, biliary cholesterol, LDL receptor of hepatocytes binding to 125 I LDL were investigated in different phases as 1 week, 2, 3, and 4 weeks groups, as well as a control group.Results In 4/10,6/10, and 7/10 cases, cholesterol gallstones were induced in 2 week, 3 week and 4 week groups respectively. The GCA bile contents decreased significantly in 3 week and 4 week groups (vs control group, P <0.05), of these, bile GDCA increased in 1 week, then gradually decreased in 2 week, 3 week and 4 week groups, and there were no significant differences among the five groups ( P >0.05). The biliary cholesterol increased greatly in 1 week, 2 week, 3 week, and 4 week gropus (vs control group, P <0.05). The Bmax values of LDL receptor of hepatocytes binding to 125 I LDL decreased signifcantly in 3 week and 4 week groups (vs 1 week and control groups, P <0.05). Kd values of those became increased in 3 week and 4 week groups (vs 1 week and control groups, P <0.05), which suggested the activity of LDL receptor decreased gradually.Conclusions Owing to the intake of high cholestrol diet with time passing by, the decreased activity of LDL receptor of hepatocytes can reduce the synthesis of GCA and secretion into the bile, which may play important roles during the formation of cholesterol gallstones.