晚期氧化蛋白产物诱导血管平滑肌细胞表达MCP-1及其信号转导通路的研究

Signal transduction of advanced oxidation protein products induced MCP-1 expressions in vascular smooth muscle cells

目的研究p38有丝分裂素激活蛋白激酶(p38 mitogen-activated protein kinase,MAPK)在晚期氧化蛋白产物(advanced oxidation protein products,AOPP)诱导的鼠血管平滑肌细胞单核细胞趋化蛋白-1表达中的作用。方法使用200和400μmol/LAOPP分别以不同时间刺激培养的鼠血管平滑肌细胞,在阻断实验中加入特异性p38MAPK阻断剂SB203580阻断p38MAPK信号转导通路。采用免疫印迹法(Western blot)检测细胞中MCP-1和磷酸化p38MAPK的表达情况。结果用特异性p38MAPK阻断剂SB203580预处理后,400μmol/LAOPP刺激4h的鼠血管平滑肌细胞MCP-1表达(平均灰度值)从42.00±0.95降至9.35±1.35受到显著抑制(P<0.01)。结论①p38MAPK信号转导途径参与了AOPP诱导的鼠血管平滑肌细胞MCP-1的表达。②晚期氧化蛋白产物促进平滑肌细胞MCP-1 mRNA和蛋白表达可能是其致动脉粥样硬化机制之一。

Objective To investigate the role of p38MAPK signaling pathway in advanced oxidation protein products （AOPP） induced expressions of monocyte chemotactic protein-1 （ MCP-1 ） in vascular smooth muscle cells （VSMCs）. Methods Vascular smooth muscle cells （VSMCs） were cultured and then co-incubated with AOPP （200,400 μmoL/L） for different time with or without the pretreatment of specific p38MAPK inhibitor SB203580. Western blot was used to detect the expression of phosphorylated p38MAPK. Results The expression of phosphorylated p38MAPK was increased after AO after stimulation, then decreased. The expression of MCP-1 SB203580 as compared pression in VSMCs and with that in the AOPP group （ P 〈 0.0 contributes to the formation of atheroscl mediated at least in part through the activation of p38MAPK PP treatment and reached the highest level 4 h was down-regulated with the pretreatment of 1 ）. Conclusion AOPP stimulates MCP-1 exerosis through this proinflammatory effect that is signaling pathway.