The Effect Of Losartan To The Expression Of Nephrin And Podocin In Podocyte Of The Diabetic Nephropathy Rats

Abjective:The main aim of this study was to investigate the expression of the nephrin and podocin in podocyte of the diabetic nephropathy(DN) rats and the mechanism of losartan-induced renal protection.Methods:54male clean level wistar rats, weight190-240g, were divided at random into normal control group(groupN), DM model group(groupDM) and losartan treatment group(groupE),each group of18. DM model group and losartan treatment group were injected the STZ into intraperitoneal to establish the model of diabetic rat. After one week of succession of the models, beginning to lavage to groupE with losartan50mg.kg-1.d-1, then the other two groups with the same volume distilled water. After4,8and12weeks of treatment,to measure the blood glucose level, body weight,serum insulin,serum creatinine, blood urea nitrogen and24h urinary protein count.24h urinary protein count was measured by Biuret method. serum creatinine and blood urea nitrogen were measured by automatic biochemical analyzer.The expressions of nephrin and podocin were detected by RT-PCR and immunohistochemist and the pathological changes of kidney were detected with optic microscope.Result:1. The contrast of the blood glucose and the serum insulin levels of three groups:Compared with the normal control group, the blood glucose of group DM and group noticeably of group DM and gtoup E increased, while the serum insulin levels decreased, with statistical significance(P<0.05).2. The contrast of the24h urinary protein count,the serum creatinine and the blood urea nitrogen of three groups:Compared with the normal control group,24h urinary protein count of group DM noticeably increased(p<0.05),but the serum creatinine and the blood urea nitrogen have no significant change. Compared with the group DM, the losartan treated group had a obvious decreased(P<0.05).3. The contrast of the expression of nephrin and podocin mRNA in podocyte of three groups:Compared with the normal control group, the expressions of nephrin and podocin mRNA in podocytes of group DM decreased(p<0.05). After treatment with losartan, the expressions of nephrin and podocin mRNA in podocytes increased(p<0.05).4. The contrast of the expression of nephrin and podocin protein in podocyte of three groups:Compared with the normal control group, the expressions of nephrin and podocin protein in podocytes of group DM decreased(p<0.05). After treatment with losartan, the expressions of nephrin and podocin protein in podocytes increased(p<0.05).5. In the renal tissues of diabetic rats, the expressions of nephrin and podocin mRNA are significantly negative correlated with the24h urinary protein.6.Kidney tissue morphology observed:Glomertular and tubular morphology rules in normal control rats, and no obvious mesangial matrix proliferation. In group DM glomerular basement membrane thickening, a large number of mesangium matrix deposition, vacuolar degeneration of tubular epithelial cells, renal interstitial fibrosis and mononuclear cells and lymphoid cell infiltration appears. After treatment with losartan,the group E pathological changes significantly reduced and significant lesions improve with time.Conclusion:The mechanism of losartan which reduced urinary protein count may act through up-regulating the expressions of nephrin and podocin.