P38信号通路对人脐静脉内皮细胞单核细胞趋化蛋白-1表达的影响

目的 探讨P38信号通路(P38MAPK)和单核细胞趋化蛋白-1(MCP-1)的关系，以及P38MAPK在糖尿病(DM)动脉粥样硬化(AS)中的作用。方法 分别以高葡萄糖(HG)、糖基化终产物(AGEs)、高胰岛素(HIns)和过氧化氢(H2O2)孵育人脐静脉内皮细胞(HUVECs)，观察HUVECs P38MAPK的蛋白表达和MCP-1 mRNA表达；以P38MAPK特异抑制剂SB203580预处理，再用以上4种刺激因素孵育HUVECs，观察MCP-1 mRNA在HUVECs的表达。结果 HG、AGEs、HIns和H2O2均可独立激活P38MAPK，使磷酸化P38MAPK蛋白表达量及MCP-1 mRNA表达量增加；SB203580预处理后，MCP-1 mRNA表达被明显抑制。结论 P38MAPK调控MCP-1的表达，表明P38MAPK可能是DM致AS发生的始动信号之一。

Effect of P38 mitogen-activated protein kinase on monocyte chemoattractant protein-1 in human umbilical vein endothelial cells

Objective To investigate the relationship between P38 mitogen-activated protein kinase (P38MAPK) and monocyte chemoattractan t protein-1 (MCP-1), in order to study the role of P38MAPK on diabetic atheros clerosis. Methods Human umbilical vein endothelial cells (HUVE Cs) were incubated with high glucose (HG), advanced glycosylation end products ( AGEs), high insulin (HIns) and H 2O 2 separately, and the expressions of phosp ho-P38MAPK and MCP-1 mRNA were detected by Western-blot and RT-PCR respe ctively. Simultaneously, HUVECs pre-treated with SB203580 (the P38MAPK special -inhibitor) were incubated with the above stimulating factors, and the expressi on of MCP-1 mRNA was detected by RT-PCR. Results HG, AGEs, HIns and H 2O 2 activated P38MAPK and increased the expressions of both phosph o-P38MAPK and MCP-1 mRNA significantly. But the expression of MCP-1 mRNA was inhibited by SB203580. Conclusions P38MAPK down-regulates the expression of MCP-1, and therefore P38MAPK may be one of initial signals on at herosclerosis.