Title: Effects of valsartan on renal interstitium fibrosis in rats after unilateral ureteral obstruction
Abstract: Objective To study the effect of valsartan,an angiotensinⅡtypeⅠreceptor antagonist(AT1RA),on renal interstitium fibrosis(RIF)in rats with unilateral ureteral obstruction(UUO),and to discuss the possible mechanisms.Methods Thirty-five Sprague-Dawley rats were randomly divided into sham-operation,model and valsartan groups.The rat UUO model was established.From the day after operation,the rats in sham-operation and model groups received intragastric valsartan and sodium chloride in tales doses.The serum creatinine(SCr),blood urea nitrogen(BUN),angiotensin-Ⅱ(AngⅡ) in blood plasma,N-acetyl-β-D-glucosaminidase(NAG)and 24 h urine β2-microglobulin(β2-MG)were examined 4 weeks after operation.The renal tissues of the obstructed sides were harvested;H-E staining and Masson staining were used to observe the tubulointerstitial lesions;and immunohistochemistry staining was used for semiquantitative analysis of alpha-smooth muscle actin(α-SMA),fibronectin(FN),plasminogen activator inhibitor-1(PAI-1),transforming growth factor-beta 1(TGF-β1),and hepatocyte growth factor(HGF).Results Compared with those in the sham-operation group,SCr,BUN,AngⅡ,NAG and β2-MG levels,and the expression of α-SMA,FN,PAI-1,and TGF-β1 in model group were significantly higher(P0.01).The levels of SCr,BUN,NAG and β2-MG were comparable between valsartan group and the model group(P0.05).The expression levels of α-SMA,FN,PAI-1,and TGF-β1 in valsartan group were significantly lower than and the expression of HGF was significantly higher than those in the model group(P0.01).Conclusion Valsartan does not improve the tubular and glomerular functions,but it can inhibit production of Ang-II.Valsartan may inhibit renal interstitial fibrosis by inhibiting renal tubule epithelial mesenchymal transdifferentiation and reducing extracellular matrix deposition through blocking up AngⅡ,inhibiting overexpression of α-SMA,FN,PAI-1,and TGF-β1,and inducing the HGF expression.
Publication Year: 2010
Publication Date: 2010-01-01
Language: en
Type: article
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