晚期糖基化终产物修饰蛋白刺激人血管内皮细胞表达粘附分子的研究

ADVANCED GLYCATION END PRODUCTS MODIFIED PROTEIN UP-REGULATES EXPRESSION OF ADHESION MOLECULES ON HUMAN ENDOTHELIAL CELLS

为探讨透析相关性淀粉样变 (DRA)时血管内皮细胞粘附分子表达上调的机制 ,采取分离正常人脐静脉内皮细胞 (HUVEC) ,将晚期糖基化终产物 (AGE)修饰的人血清白蛋白 (AGE HSA)、人血清白蛋白 (HSA)与HUVEC在体外共同培养的方法 ,并用荧光单克隆抗体染色 ,流式细胞仪定量检测内皮细胞表面细胞间粘附分子 1(ICAM 1)、血管细胞间粘附分子 1(VCAM 1)、E 选择素 (E selectin)的表达。结果显示 ,正常人脐静脉内皮细胞表达ICAM 1和VCAM 1,但无E selectin的基础表达。AGE HSA能以时间和剂量依赖的方式上调血管内皮细胞粘附分子ICAM 1、VCAM 1、E selectin的表达 (P <0 .0 5 ) ,而HSA对血管内皮细胞上述粘附分子的表达均无影响。提示AGE能上调血管内皮细胞粘附分子的表达 ,从而促进DRA时单核 /巨噬细胞的浸润。

Enhanced expression of adhesion molecules on human endothelial cells of synovial tissue has been demonstrated in patients with dialysis related amyloidosis(DRA).The study was conducted to elucidate the mechanism by which the expression of adhesion molecules on human endothelial cells was up regulated. Human endothelial cells derived from umbilical veins(HUVEC) were coincubated in vitro with native human serum albumin(HSA) or HSA modified with advanced glycation end products(AGE HSA).The expression of adhesion molecule intercellular adhesion molecule 1(ICAM 1),vascular cell adhesion molecule 1(VCAM 1) and E selectin was determined respectively by immunofluorescence staining and flow cytometer analysis.The results showed that ICAM 1 and VCAM 1, but not E selectin,were constitutively expressed on HUVEC. AGE HSA enhanced the expression of ICAM 1, VCAM 1 and E selectin on HUVEC in a time and dose dependent manner. HSA had no effect on the expression of adhesion molecules. The results led to the conclusion that AGE HSA up regulated the expression of adhesion molecules on human endothelial cells and therefore promoted the infiltration of monocytes/macrophages around β 2 microglobulin amyloid.