The Mechanism Of Podocyte Injury Factors Nephrin And Desmin In The Renal Damage Of Hyperuricemia

Objectives To establish a hyperuricemia rat model and intervene with febuxostat and allopurinol to investigate the role of podocytes and related molecules in the pathogenesis of renal damage in hyperuricemia by detecting the expression of nephrin,desmin and ?-SMA,which can provide evidence for early intervention and treatment of clinical hyperuricemia nephropathy.Methods Thirty-two Sprague-Dawley rats were randomly divided into four groups: normal control group(NC),model group(HUA),febuxostat group(FX)and allopurinol group(Allo),with 8 rats in each group.All rats were received potassium oxazinate and adenine by gastric gavage once a day to induce hyperuricemia except NC group.FX and ALLO group were dividedly received febuxostat(8 mg/kg/d)and allopurinol(50 mg/kg/d)at the same time.NC group were given the same value of 0.5% CMC-Na.Renal function(BUN,Cr,UA,24h-UTP)were measured at week 0,4 and 8.At the end of the 8th week,kidney histomorphological were measured to evaluate the degree of renal damage.The expressions of markers for podocyte injury(nephrin,desmin)and epithelial mesenchymal transition(EMT)change of renal tubular epithelial cells(?-SMA)were detected by Immunohistochemistry,Western blot and RT-PCR.Results (1)At 4 and 8 weeks,the levels of BUN,Cr,UA and 24h-UTP of HUA group were higher than those in NC group(P<0.05 or 0.01);(2)HE staining showed that renal damage in the HUA group was obvious,and it was ameliorated after treatment with febuxostat;Masson staining showed that renal tubular epithelial cells had the most severe fibrosis in HUA group,and FX group were lower than those in the ALLO group.The transmission EM observations showed that podocytes were widely fused in the HUA group.The degree of podocyte lesions in FX group was lower than those in ALLO and HUA group,and the difference didn't have significant differences statistically compared with NC group.(3)The results of immunohistochemistry,Western blot and RT-PCR indicated that renal tissue in NC group hardly expressed ?-SMA and desmin,but highly expressed nephrin;In HUA group,?-SMA and desmin were highly expressed and nephrin was lowly expressed.Compared with ALLO group,the expression of ?-SMA and desmin in FX group was significantly reduced(P<0.01),the expression of nephrin was increased(P<0.01),These change were similar to those in NC group,and there was no significant difference statistically between NC and HUA group(P>0.05).Conclusions Hyperuricemia can cause podocyte injury and renal tubular epithelial cells fibrosis.Febuxostat treatment can reduce podocyte injury and improve renal damage through reducing the uric acid level in hyperuricemia rats.