糖基化低密度脂蛋白受体途径代谢与动脉粥样硬化关系的实验研究

EXPERIMENTAL STUDY OF GLUCOSYLATED LOW DENSITY LIPOPROTEIN PATHWAY AND ATHEROSCLEROSIS

本文旨在观察低密度脂蛋白(LDL)糖基化对其受体途径代谢的影响。以密度梯度超速离心法分离人血清LDL,经聚丙烯酰胺凝胶电泳鉴定纯度后用一氯化碘法将其标记成^(125)I-LDL。在培养的人成纤维细胞上进行LDL放射受体分析并检测细胞内总胆固醇含量。该受体最大高亲和性结合(Bmax)为47ngLDL/mg细胞蛋白,亲和常数(Km)为9.4μg/ml。糖基化LDL的受体结合、摄入和降解值显著低于对照LDL(P<0.01),而糖基化LDL孵育的细胞,其总胆固醇含量却明显增高(P>0.01)。结果提示,LDL糖基化可能是糖尿病人易患脂代谢障碍和动脉粥样硬化的重要机制。

This study was designed to assess effect of low density lipoprotein (LDL)glucosylation on its pathway. Human serum LDL was isolated by density gradient ultracentifugation and its purity was identified, by polyacrylamide gel electrophoresis, LDL was radioiodinated with ^(125)Ⅰ by iodine monochloride, LDL radioreceptor assay was performed and intracellular total cholesterol was determined in cultured human fibroblasts, The maximal high affinity binding(Bmax) of the receptor was 47 ng LDL/mg cell protein, the km value was 9.4μg/ml. The receptor mediated binding, internalization and degradation of glucosylated LDL were significantly decreased compared with those of control LDL, but total cholesterol centent of cultured fibroblasts incubated, with glucosylated LDL was significantly higher than that incubated with control LDL. The results suggest that glucosylation of LDL might be one of the impcrtant mechanisms for high incidence of disturbed lipid metabolism and atherosclerosis in diabetic patients.