p38丝裂原活化蛋白激酶对HBZY-1系膜细胞株表达NF-κB和MCP-1的调控

目的 探讨p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase, p38MAPK)与NF-κB、单核细胞趋化蛋白1(monocyte chemoattractant protein-1, MCP-1)之间的关系,从而研究p38MAPK和NF-κB、MCP-1在糖尿病肾病中的作用机制.方法 分别以高葡萄糖、高胰岛素、H2O2和糖基化终产物孵育大鼠肾小球系膜细胞株HBZY-1;先以p38MAPK特异抑制剂SB203580预处理细胞株HBZY-1,再给予上述4种因素孵育细胞株HBZY-1,观察其p38MAPK和NF-κB、MCP-1的表达.结果 高葡萄糖、高胰岛素、H2O2和糖基化终产物均可独立激活p38MAPK,使其磷酸化表达量增加,NF-κB、MCP-1表达也明显增加;SB203580预处理后,NF-κB、MCP-1表达被显著抑制.结论 p38MAPK可能通过激活NF-κB、MCP-1而诱导糖尿病时肾脏的损害,p38MAPK和NF-κB、MCP-1在糖尿病肾病的发生发展过程中可能起重要作用.

A role of p38 mitogen-activated protein kinase in regulation of NF-κB and MCP-1 expressions in HBZY-1 mesangial cell line

Objective To investigate the relationship among p38 mitogen-activated protein kinase (p38MAPK), NF-KB and monocyte chemoattractant protein-1 (MCP-1), and to study the role of p38MAPK, NF-κB and MCP-1 in diabetic nephropathy. Methods Protein expressions of p38MAPK and NF-κB, and mRNA expression of MCP-1 were initially investigated in rat mesangial cell line HBZY-1, which were incubated separately with 25mmol/L glucose, 100nmol/L insulin, 100 μmol/L H2 O2 and 100mg/L advanced glycosylation end products (AGEs). The relationship among p38MAPK, NF-κB and MCP-1 expression Was observed by usingSB203580, a specific inhibitor of p38MAPK. Results The expressions of p38MAPK, NF-κB and MCP-1 were increased in HBZY-1 cells incubated separately with 25mmol/L glucose, 100nmol/L insulin, 100μmol/L H2 O2and 100 mg/L AGEs. Expressions of NF-κB and MCP-1 were significantly reduced when p38MAPK was inhibited by SB203580. Conclusion p38MAPK, NF-κB and MCP-1 are involved in development of diabetic nephropathy, and p38MAPK stimulation is essential for the expressions of NF-κB and MCP-1.