The Change Of Toll Like Receptor4Expression In The Renal Tissue Of Rats With Diabetic Nephropathy And The Effect Of Irbesartan On The Expression

Objective:To investigate the changes of toll-like receptor4(TLR4), myeloid differentiationfactor88(MyD88), interleukin-1(IL-1), macrophages chemotaxis protein-1expressionand the effect of irbesartan on the expression in rats with diabetic nephropathyexplore the possible role of TLR4in diabetic nephropathy(DN).Method:Male SD rats were randomly divided into three groups as follows: normal controlgroup (NC), model control group(MC) and irbesartan treated group(ARB). Modelgroup were induced to be diabetic nephropathy by intraperitoneal injection withstreptozotici(nSTZ)after4weeks high glucose and fat diet. Serum creatinine,glucoseand24h urine protein were determined at week2,4,6and8respectively. Thetransmutation of renal pathomorphology was observed and renal protein expression ofTLR4was detected by immunohistochemical method at week4and8. Serum proteinexpression of MCP-1and IL-1were detected by enzyme-linked immuno sorbent assay(ELISA).mRNA expression of TLR4and MyD88were detected by real timequantitative polymerase chain reaction(Real-Time PCR) at week4and8.Result:The TLR4protein was mainly expression in the plasma of glomerulus and renaltubular epithelial cells,it is markedly increased in MC group and ARB groupcompared with NC group.There has statistical significance between ARB group andMC group at week8. At4,8week, the plasma concentration of MCP-1,IL-1of therats were raised up obviously in group MC and group ARB.Compared with MCgroup, ARB group reduced the protein at week8and has statistical significance.(P<0.05).As real time-PCR shows, mRNAleval of TLR4and MyD88has statisticalsignificance (P<0.05)between MC,ARB group and NC group.At8week comparedwith MC,ARB has reduced the expression and have statistical significance. Positivecorrelation is found between TLR4expression and Inflammatory reaction degree,thesame correlation also existed between TLR4expression and degree of renal function. Conclusion:TLR4and it's signal pathway possibly via adjustment inflammatory reaction toplay a pivotal role in the pathogenesis of renal damage in diabetic nephropathy.Irbesartan may delay DN progress through reduce expression of TLR4.