兔胆囊结石形成过程中肝细胞低密度脂蛋白受体变化的研究

The LDL Receptor Activity of Hepatocytes During Cholesterol Gallstone Formation in Rabbits

为从脂蛋白胆固醇代谢的分子受体水平探讨胆囊胆固醇结石的成因，作者采用高胆固醇膳食建立兔胆囊胆固醇结石模型，而后对进食高胆固醇膳食后１、２、３、４周组及对照组肝细胞低密度脂蛋白（ＬＤＬ）受体活性变化进行了动态研究。结果发现：高胆固醇膳食后１周开始出现胆囊结石，２、３、４周组分别有４／１０、６／１０和７／１０只兔出现胆囊结石；１２５Ｉ－ＬＤＬ与肝细胞ＬＤＬ受体最大结合力在１周组略升高（Ｐ＞０．０５），２周组逐渐下降，３周和４周组明显下降（Ｐ＜０．０５）；解离常数Ｋｄ值逐渐升高，以３周和４周组明显（Ｐ＜０．０５）。由此提示：随着高胆固醇膳食进食时间延长，肝细胞ＬＤＬ受体活性下降，致血清ＬＤＬ清除受阻和胆汁中胆酸减少，可能在胆囊胆固醇结石形成过程中起着重要作用。

In order to study the mechanism of cholesterol gallstone formation through rabbit model which was induced by high cholesterol diet, we investigated the LDL receptor activity of hepatocytes binding to 125ILDL in different phases, namely 1,2,3 week group and 4 week, and in a control group besides. In this animal experiment, cholesterol gallstones were induced at 2week, 3week and 4week groups in 4/10, 6/10, and 7/10 cases respectively. The Bmax values of LDL receptor of hepatocytes binding to125ⅠLDL decreased signifcantly in 3week and 4week groups(vs 1week and control groups, P<0.05). The kd values became increased in 3week and 4week groups (vs 1week and control group, P<0.05), which suggested that the activity of LDL receptor decreased gradually. In conclusions owing to the intake of high cholesterol diet with the passage of time, the decreased activity of LDL receptor of hepatocytes would reduce the synthesis of bile acid.