晚期糖基化终产物刺激单核细胞产生活性氧的信号传导机制

Mechanisms of Advanced Glycation End Products-induced Production of Reactive Oxygen Species in Monocytic Cells

目的 :探讨晚期糖基化终产物(advanced glycation end products,AGE)诱导单核细胞产生活性氧的机制。方法采用密度梯度离心法分离健康成人外周血单核细胞,经AGE修饰的人血清白蛋白(AGE-HSA)刺激后,用化学发光法测定活性氧(reactive oxygen species,ROS)的生成;分别应用超氧化物歧化酶(SOD)、NADPH氧化酶特异性抑制剂apocynin、抗AGE受体(RAGE)抗体预处理单核细胞,观察AGE-HSA刺激单核细胞生成ROS的变化。结果 AGE-HSA可以诱导单核细胞产生ROS。SOD可以有效的清除AGE刺激单核细胞后分泌的大量的ROS;抗RAGE抗体、apocynin通过阻断AGE与RAGE的结合及抑制NADPH氧化酶的活性可以有效地抑制ROS产生。结论 AGE可通过RAGE激活NADPH氧化酶产生ROS。

ObjectiveTo find the mechanisms of advanced glycation end products（AGE）-induced production of reactive oxygen species（ROS） in monocytic cells.MethodsHealthy human blood monocytes were isolated by Ficoll-hypaque gradient centrifugation.The production of ROS stimulated by AGE-modified human serum albumin（AGE-HAS） was determined by chemiluminescence.The changes in ROS production were detected after treatment with superoxide dismutase（SOD）,apocynin and anti-receptor for AGE（RAGE） antibody.ResultsAGE-HSA induced ROS production and SOD eliminated ROS in monocytic cells treated with AGE.In addition,anti-RAGE antibody and apocynin inhibited ROS production by interrupting AGE-RAGE interaction and by blocking NADPH oxidase activity,respectively.ConclusionAGE can induce ROS production through RAGE-induced activation of NADPH oxidase.