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探讨晚期糖基化终产物(AGE)修饰蛋白对内皮细胞生成白介素8(IL-8)的作用,及晚期糖基化终产物受体(RAGE)在此病理过程中的作用.内皮细胞来自培养的人脐静脉内皮细胞(HUVEC).将内皮细胞与不同浓度的AGE修饰人血清白蛋白(AGE-HSA)在体外共同培养,或以可溶性晚期糖基化终产物受体(sRAGE)对AGE-HSA进行预处理后再与HUVEC共同培养.用蛋白质液相芯片法检测HUVEC培养上清中IL-8水平,并提取细胞RNA,进行RT-PCR反应,检测细胞中IL-8mRNA的表达水平.结果表明,AGE-HSA以时间和剂量依赖的方式刺激HUVEC生成IL-8,未经修饰的HSA无此作用.AGE-HSA用sRAGE预处理后,刺激HUVEC生成IL-8的作用被抑制,并且此抑制作用呈剂量依赖的方式.AGE-HSA刺激HUVEC使IL-8mRNA表达增高,未经修饰的HSA无此作用.sRAGE能够阻断AGE-HSA诱导HUVEC表达IL-8mRNA的作用.整个变化趋势与蛋白质水平一致.研究首次证实,AGE-HSA与细胞表面受体RAGE相互作用可刺激内皮细胞分泌IL-8,并上调IL-8mRNA的表达.这为研究加速型血管病变的发病机制提供了新视角,也为治疗由AGE增多和潴留所引起的病理损害提供了新靶点.
To investigate the effect of advanced glycation end products (AGE) modified proteins on the production of interleukin-8 (IL-8) by endothelial cells and the role of advanced glycation end-products receptor (RAGE) in this pathological process.Endothelial cells from culture Of human umbilical vein endothelial cells (HUVECs) were cultured in vitro with different concentrations of AGE-modified human serum albumin (AGE-HSA) or with soluble advanced glycation end-products receptor (sRAGE) HSA were pretreated with HUVEC and incubated with HUVEC.The level of IL-8 in the supernatant of HUVECs was detected by protein liquid-chip method and the RNA was extracted and RT-PCR was performed to detect the expression of IL-8mRNA in the cells.Results The results showed that AGE-HSA stimulated HUVEC to produce IL-8 in a time-and dose-dependent manner, without the effect of unmodified HSA.After pretreatment with sRAGE, the effect of stimulating HUVEC to produce IL-8 was inhibited HSA stimulated HUVEC to up-regulate the expression of IL-8mRNA without the effect of unmodified HSA.RAGE blocked the effect of AGE-HSA-induced expression of IL-8mRNA in HUVEC.The overall trend was similar to that of protein Level consistent. The study for the first time confirmed that AGE-HSA and cell surface receptors RAGE interaction stimulates the secretion of IL-8 by endothelial cells and up-regulates the expression of IL-8 mRNA, which provides a new perspective for studying the pathogenesis of accelerated angiopathy and also provides a method for the treatment of pathological damage caused by AGE increase and retention New target