The Effect And Mechanism Of Epalrestat On The Deposition Of Extracellular Matrix Induced By High Glucose

[OBJECTIVE]To observe the effect of Aldose Reductase,PKC, Fibronectin in extracellular matrix induced by different high glucose on mesangial cells and observe the change of these tagets above-mentioned after intervened by Epalrestat , study The Effect and Mechanism of Epalrestat on the deposition of extracellular matrix induced by high glucose[METHODS] 1. Mesangial cells were cultured in different glucose(5.6mmol/L control group,15mmol/L,20mmol/L,25mmol/L). The mRNA of Reductase and Fibronectin was detected by semi-quantitative reberse transcription polymerase chain reaction (RT-PCR). Aldose Reductase activity was detected by ultraviolet specrophotometer. Protein levels of pkc was detected by Western blot. On this basis,choose glucose 25mmol/L culture Mesangial cells,use Epalrestat intervened cells cultured in high glucose(25mmol/L),detecte the tagets above-mentioned,in order to investigate Epalrestat's(0.1μmol/L,1μmol/L,10μmol/L) effect on extracellular matrix induced by high glucose(25mmol/L) on glomerular mesangial cells[RESULTS]Compare with normal glucose(5.6mmol/L),as the increase of glucose concentration ,The mRNA of Reductase and Fibronectin show enhanced expression,Aldose Reductase activity gradually increase,the protein levels of pkc also dose-dependently increase. The effect of these tagets induced by high glucose can be inhibited being treated 36 hours with Epalrestat,and having a dose dependent effect.[CONCLUSIONS] 1. high glucose increased the mRNA of FN and and it had dose dependent effect.high glucose increased extracellular matrix,the mechanism of action may be through induce enhanced expression of AR and PKC. use Epalrestat intervened cells cultured in high glucose(25mmol/L) can decreased extracellular matrix expression induced by high glucose and had dose dependent effect,Epalrestat can protect the kidney from decreased expression of AR and PKC , thus decreased extracellular matrix expression.