Effects of valsartan on renal interstitium fibrosis in rats after unilateral ureteral obstruction
10.3724/SP.J.1008.2010.00278
- Author:
Jian-Song ZHOU
1
Author Information
1. Department of Nephrology, Third Affiliated Hospital, Nantong University
- Publication Type:Journal Article
- Keywords:
Alpha-smooth muscle actin;
Angiotensin II;
Renal interstitium fibrosis;
Unilateral ureteral obstruction
- From:
Academic Journal of Second Military Medical University
2010;31(3):278-282
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of valsartan, an angiotensin II type I receptor 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 (Ang II ) 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, Ang II, NAG and (β2- MG levels, and the expression of α-SMA, FN, PAI-l, and TGF-β1 in model group were significantly higher(P<0. 01). The levels of SCr, BUN, NAG and β22-MG were comparable between valsartan group and the model group(P>0. 05). The expression levels of orSMA, FN, PAI-l, and TGF-β1 in valsartan group were significantly lower than and the expression of HGF was significantly higher than those in the model group(P<0. 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 Ang Q, inhibiting overexpression of α-SMA, FN, PAI-l, and TGF-β1, and inducing the HGF expression.
