【摘要】 目的探讨P38促分裂原活化蛋白激酶(P38MAPK)信号通路在糖尿病肾病(DN)中的作用及辛伐他汀(SI)在防治DN中的作用机制。方法分别以高糖、糖基化终产物(AGE)或过氧化氢体外孵育大鼠肾小球系膜细胞(MC),检测P38MAPK和单核细胞趋化蛋白1(MCP-1)及细胞间黏附因子1(ICAM-1)在MC的表达。比较有无P38MAPK特异性抑制剂SB203580(SB)或辛伐他汀(SI)预处理时以上3种因素对P38MAPK和MCP-1及ICAM-1在MC表达的影响。结果高糖、AGE或H2O2均可独立激活P38MAPK,并增加MCP-1及ICAM-1在MC的表达;SB显著抑制MCP-1及ICAM-1的表达;SI抑制P38MAPK的活化并减少MCP-1及ICAM-1的表达。结论P38MAPK是MCP-1及ICAM-1的上游信号分子,表明P38MAPK可能是DN发生的始动信号之一。SI可能通过抑制P38MAPK磷酸化而抑制MCP-1及ICAM-1的表达,有防治DN的作用。更多还原

【Abstract】 Objective To explore the effect of P38 mitogen-activated protein kinase(P38MAPK)on diabetic nephropathy(DN)and the mechanism of simvastatin-prevented development of DN.Methods Rat mesangial cells(RMC)were incubated with high glucose(HG),advanced glycosylation end products(AGE)or H2O2 with or without pre-treatment with SB203580(P38MAPK specific inhibitor)or simvastatin(SI).The expressions of pho-P38MAPK,monocyte chemoattractant protein-1(MCP-1)and intercellular adhesion molecule-1(ICAM-1)in MC were detected by Western-blot or RT-PCR.Results HG,AGE or H2O2 were able to activate P38MAPK and increase the expressions of MCP-1 and ICAM-1 in RMC.The expressions of MCP-1 and ICAM-1 were inhibited by SB203580.SI inhibited the activation of P38MAPK and reduced the expressions of MCP-1 and ICAM-1.Conclusions P38MAPK is an upstream signaling molecule of MCP-1 and ICAM-1.P38MAPK may be one of the initiating signals of DN.SI can inhibit the expressions of MCP-1 and ICAM-1 by repressing P38MAPK signaling pathway and therefore prevent the development of DN.更多还原