| Objective: Renal interstitial fibrosis is the common feature in various chronic renal damage,and it represents the common approach for various renal diseases to develop chronically to end-stage renal failure.Many studies indicate that the progression of renal interstitial fibrosis is correlated with the expression and more activation of transforming growth factor-β1 (TGF-β1).As a major activator of transforming growth factor-β1 (TGF-β1),Thrombospondin-1(TSP-1) has been drawing more and more attention in the field of renal disease .Mesangial cells in vitro studies found that the activation of TGF-β1 which is induced by angiotensin II (Angiotensin II, AngII) is mediated by TSP-1, AngII type 1 receptor blockers can inhibit TSP-1 AngII-induced secretion. In this study, losartan is used in renal interstitial fibrosis model in rats,to observe the expression of TSP-1,TGF-β1 and ColⅢin the renal Interstitium of rats with unilateral ureteral obstruction (UUO),and to investigate the protective effects of losartan on renal tubulointerstitial fibrosis and its possible mechanism.Methods:45 healthy male SD rats,weighting (200±10) g,were randomly divided into 3 groups: sham-operated group (group A),unilatersl ureteral obstruction group (UUO;group B), UUO with losartan treated group(group C,) (n=15 per group).Under Chloral Hydrate anesthesia (0.1ml/Kg body wt,i.p),the left ureter was ligated by 4.0 silk at two points and cut between the ligatures in order to prevent retrograde urinary tract infection.Sham-operated group had their ureters manipulated but not ligated.All rats were allowed free access to food and water.Animals in group C were treated with losartan (50 mg / kg / d) 24 hours before surgery while the sham group and the UUO group received equal volume slain at the same time.Rats were killed at days 3,7 and 14 after surgery.And kidney tissues were removed and subjected to the following experiments.HE and Masson staining was used to observe the pathological changes;Immunochemistry was used to analyze the renal expression of TSP-1,TGF-β1 and ColⅢ.The results were analyzed semi-quantitatively by the pathological image analysis system.All the data were analysed by SPSS10.0 statistics software,P value<0.05 was considered to have statistical significance.Results: 1.Pathological changes:there was no predominant changes in group A in light microscopy using the staining mathods of HE and Masson.There were different degrees of interstitial fibrosis,interstitial leukocyte infiltration,tubular dilation and the relative area of renal tubulointerstitium expantion in group B at day3,day7 and day14 after UUO.The relative area of renal tubulointerstitium was significantly increased in the obstructed kidneys compared with that of group A(P<0.05).However,the relative area of renal tubulointerstitium of group C significantly decreased compared with that of group B(P<0.05).2.immunohistochemical staining:the level of TSP-1 was low in the renal tubules and glomeruli in group A,and mainly distributed in the cytoplasm of renal tubular epithelial cells.While the level of TSP-1 in group B was significantly increased than that of group A.In group C, the level of TSP-1 was lower than that of group B at the same time point(P<0.05).The expression of TGF-β1 was occasionally found in group A,and the expression was graduately increased in group B. In group C, the level of TGF-β1 was lower than that of group B at the same time point(P<0.05).ColⅢin Group A only trace expressed in the arteries around,and had a small quantity of expression in renal interstitial.ColⅢdistributed like a brown cord in renal interstitial in Group B,and increased with the extension of time for obstruction.(P <0.05).In group C, the level of ColⅢwas lower than that of group B at the same time point(P<0.05).The protein level of TSP-1was significantly associated with TGF-β1 and ColⅢ.Conclusion: The expression of TSP-1 was low in the interstitial of normal rat kidney,and significantly increased during interstitial fibrosis,and correlated with the expression of TGF-β1 and ColⅢ. AngII type 1 receptor antagonist (losartan) can decrease the expression of TSP-1,TGF-β1,ColⅢin interstitial and delay the progression of renal interstitial fibrosis.
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