| Objective:The present study aimed to investigate whether Rho-kinase inhibitor fasudil might improve renal function and histology in5/6nephrectomized rat model of chronic renal failure. We examined renoprotective effect of fasudil and compared further with angiotensin II type2receptor antagonists CS-866.Methods:Male SHR rats underwent5/6nephrectomized were randomly assigned to receive vehicle (control group), fasudil (FA group,10mg/kg/day), and CS-866treatment (CS-866group,10mg/kg/day). Sharn group was underwent sham operation at the same time. Serum creatinine (Scr), blood urea nitrogen (BUN), and urinary protein excretion (UPE) were measured. Kidney histomorphology was studied by PAS staining and an index of glornerulosclerosis (GSI) was evaluated. In addition, macrophage infiltration (ED1), a-SMA, and WT1were also examined by immunohistochemistry.Results:(1) UPE in the control group were significantly higher than that in sham group (p<0.0001vs. sham). FA group and CS-866group showed significant decrease in UPE compared with the control group (p<0.01FA vs. control;p<0.001CS-866vs. control);(2) The level of Scr and BUN in the control group were significantly higher than that in the sham group (p<0.0001vs.sham). CS-866treatment significantly decreased the level of Scr (p<0.05vs.control), whereas FA had no effect on Scr;(3) The GSI values in the control group was significantly higher than in the sham group(p<0.001vs.sham). However, the GSI values in the FA and CS866group were significantly lower than that in the control group(p<0.001vs.control);(4) The number of the ED1positive cells in glomerular in the control group was significantly higher than that in the sham group(p<0.001vs.sham). FA group and CS-866group showed significant decrease in the number of the ED1positive cells in the glomerulus (p<0.001vs.sham);(5) The expression of the α-SMA in the glomerular mesangium in the control group were significantly higher than that in the sham group (p<0.001vs.sham) and these were significantly decreased in FAand CS-866groups compared with control group (p<0.001vs.control);(6) The number of the WT1positive cells in the control group were significantly lower than in the sham group(p<0.001vs.sham) and this was significantly increased in the FA and CS-866groups compared with control group (p<0.001vs.control).Conclusion:(1) In5/6nephrectomized SHR rats of chronic renal failure model, we found that Rho-kinase inhibitor fasudil could inhibit activation of Rho/Rho-kinase pathway, decrease of the UPE, and improved renal function.(2) In5/6nephrectomized SHR rats of chronic renal failure model, Rho-kinase inhibitor fasudil could reduce glomerulosclerosis, inhibit macrophage infiltration in glomeruli, and inhibit mesangial or podocyte phenotype transition.(3) Rho-kinase inhibitor fasudil had similar renoprotective effects with Ang Ⅱ receptor antagonist in5/6nephrectomized hypertensive rats. |
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