【摘要】 目的探讨C反应蛋白(CRP)对单核细胞妊娠相关血浆蛋白A(PAPP-A)蛋白和基因表达的影响及其机制。方法采用密度梯度离心法分离人外周血单核细胞,分别采用Western blot和实时荧光定量聚合酶链反应方法观察CRP刺激单核细胞PAPP-A蛋白和mRNA表达的时间及剂量效应。采用Active Motif的专利技术测定CRP对单核细胞核转录因子κB(NF-κB)活性的影响。同时观察给予NF-κB抑制剂BAY11-7082预处理后,CRP对单核细胞PAPP-A表达的影响。结果 CRP(20 mg/L)刺激单核细胞2 h后,PAPP-A的蛋白和mRNA表达开始增加,呈时间依赖性,同时呈剂量依赖性诱导单核细胞的PAPP-A表达。CRP可显著增加单核细胞NF-κB p65水平,在给予NF-κB抑制剂BAY11-7082预处理后,CRP诱导PAPP-A表达的作用受到抑制。结论 CRP可通过激活NF-κB上调单核细胞PAPP-A的蛋白和基因表达,这可能是急性冠状动脉综合征患者循环中PAPP-A升高的机制之一。更多还原

【Abstract】 Objective To investigate the effects of C-reactive protein(CRP) on pregnancy associated plasma protein-A(PAPP-A) protein and mRNA expression in human peripheral blood mononuclear cells(PBMCs) and the underlying mechanism. Methods Human PBMCs were obtained from healthy volunteers by Ficoll-paque centrifugation.PAPP-A protein and mRNA expression in PBMCs after stimulated with CRP were measured by western blotting and RT-PCR respectively.The content of NF-κB p65 was assayed with the patented method of Active Motif.In addition,the effect of CRP on PAPP-A expression after pretreatment with BAY11-7082 was investigated. Results PAPP-A protein and mRNA levels were increased in time-and dose-dependent manner 2 hours after CRP(20 mg/L) stimulation.NF-κB p65 in PBMCs was significantly increased after CRP stimulation.The expressions of PAPP-A protein and mRNA induced by CRP were significantly inhibited by NF-κB inhibitor(BAY11-7082). Conclusions PAPP-A expression in human PBMCs might be regulated by CRP through NF-κB pathway.更多还原