肝素对血液透析病人单核细胞表面晚期糖基化终产物受体的影响  

Heparin blocks the binding of advanced glycation end products to its receptors on human monocytes

作　　者：任昊[1] 侯凡凡[1] 张训[1] 

机构地区：[1]第一军医大学南方医院肾脏科解放军肾脏病研究所,广州510516

出　　处：《中华内科杂志》2002年第1期43-46,共4页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金资助项目 ( 39770 349)

摘　　要：目的　研究肝素对慢性肾衰竭长期血液透析 (血透 )病人单核细胞表面晚期糖基化终产物 (AGE)受体的影响 ,探讨血透病人体内AGE潴留的机制。方法　用核素 [12 5I]标记AGE修饰的人血清白蛋白 (AGE HSA)。用密度梯度离心法分离人外周血单核细胞。用放射性配体 受体结合法观察肝素和低分子量肝素对血透病人及正常人单核细胞表面AGE受体的影响。结果　采用常规持续肝素输注法进行抗凝的血透病人 ,在透析后 15min ,单核细胞与12 5I AGE HSA的结合被抑制 2 7%,作用持续 6h ,透析后 2 4h结合率恢复至透析前水平 ;用低分子量肝素抗凝的病人 ,透析中及透析后单核细胞与12 5I AGE HSA的结合无明显变化。体外实验显示 ,肝素抑制AGE与其单核细胞表面AGE受体的结合 ,这种作用呈剂量依赖性 ;低分子量肝素对AGE受体不具有封闭作用。结论　肝素可以阻断AGE与其单核细胞表面AGE受体的结合 ,从而干扰体内AGE的清除 ,可能是造成血透病人体内AGE潴留的原因之一。Objective Previous studies have demonstrated the accumulation of advanced glycation end products (AGE) in patients with chronic renal failure (CRF), but the mechanism is not completely understood. This study was performed to elucidate the effect of heparin on binding of AGE to its receptors on human monocytes. Method Human serum albumn (HSA) modified with AGE was prepared in vitro and was radioiodinated with carrier-free [ 125 I]. Human peripheral blood monocytes obtained from dialysis patients and normal volunteers were isolated by Ficoll-hypaque centrifugation technique. Specific binding 125 I-AGE-HSA to the AGE-receptor on human monocytes was measured by radioactive ligand-receptor binding assay.Result The binding of 125 I-AGE-HSA to its receptors in dialysis patients was inhibited by 27% 15 minutes after starting of hemodialysis using heparin as anti-coagulant. These effects continued 6 hours and resume to the levels of predialysis after 24 hours. There was no differences in binding of 125 I-AGE-HSA to monocytes between pre-and post-dialysis session when low-molecule weight heparin (LMWH) was used as the anti-coagulant. In vitro study further demonstrated that exposure of normal monocytes to heparin-containing media inhibited the binding of 125 I-AGE-HSA to its receptor with a dose-dependent manner. LMWH did not inhibit such binding.Conclusion Heparin blocks the binding of AGE to its receptors on monocytes and may therefore interrupt the clearance and degradation of AGE. This may be one of the mechanisms by which AGE accumulation occurs in patients with hemodialysis.

关 键 词：肝素 单核细胞 糖基化终产物受体 血液透析 肾功能衰竭 

分 类 号：R459.5[医药卫生—治疗学]