Abstract: AIM:To investigate the effects of fenofibrate (FB)and rosiglitazone(RG)on the signal passway of p38 mitogen-activated protein kinases (p38 MAPK)in glomerular mesangial cells cultivated in high concentration of glucose. METHODS:Rat mesangial cells(MC)were incubated in 5. 5 mmol/L normal control glucose, 25 mmol/L high glucose (HG), HG + 100 μmol/L fenofibrate (FB +HG), HG +20 μmol/L rosiglitazone maleate (RG +HG), respectively. The fibronectin (FN)and type Ⅳ collagen (Col-Ⅳ)in supernatant were determined by ELISA. The expressions of p38MAPK and phospho-p38MAPK proteins in cytoplasm and nuclei were detected by Phospho-ELISA. The mRNA expression of p38MAPK was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).RESULTS:Compared with normal control, the Col-Ⅳand FN in supernatant in HG group were much higher, the expression of p-p38MAPK was increased in cytoplasms and nuclei. Col-Ⅳ and FN were obviously decreased with the treatment of FB or RG, and the expression of p-p38MAPK in nuclei was down-regulated, but the expression of p-p38MAPK in intracytoplasm had no changes. There were no significant differences of the expressions of total protein and mRNA of p38MAPK among four groups. CONCLUSION: FB, RG could inhibit the activation of p38MAPK in nuceli of MC cultivated in high concentration of glucose, and then reduce the synthesis of extracellular matrix.

Key words: fenofibrate, rosiglitazone, mesangial cells, p38 mitogen-activated protein kinases (p38 MAPK), diabetic nephropathy