Objective:To investigate the relationship between p38 mitogen-activated protein kinase(p38MAPK) and vascular endothelial growth factor (VEGF)

and to study the role of p38 mitogen-activated protein kinase and vascular endothelial growth factor for diabetic nephropathy

and therefore to study the mechanism of sodium selenite in anti-diabetic nephropathy.Methods:We initially investigated protein expression of p38MAPK and VEGF in rat mesangial cells(RMCs)which were incubated respectively with 25 mmol/L glucose

100mg/L BSA-AGEs

100nmol/L insulin and 100 μmol/L H 2O 2.We also studied the relationship between p38MAPK and VEGF protein expression by using SB203580

a specific inhibitor of p38MAPK.We then evaluated the direct effects of sodium selenite on the regulation of p38MAPK and VEGF protein expression.Results:p38MAPK and VEGF had significantly higher expression in RMCs incubated with 25mmol/L glucose

100mg/L BSA-AGEs

100nmol/L insulin and 100μmol/L H 2O 2 respectively.VEGF activity was significantly reduced when p38MAPK was inhibited by SB203580.Furthermore

both p38MAPK and VEGF protein expression were significantly decreased in RMCs with sodium selenite treatment.Conclusion:p38MAPK and VEGF are involved in development of diabetic nephropathy and p38MAPK stimulation is essential for VEGF expression

and also suggests that sodium selenite may play a role in the prevention of diabetic nephropathy by down-regulation of both p38MAPK and VEGF expression.