| ObjectiveThe model of unilateral ureteral obstruction was established to observe renal interstitial fibrosis of young rats.And then the rats were cured by recombinant human erythropoietin (EPO). To detect the expression levels and changes of a-smooth muscle actin (a-SMA), transforming growth factor-β1(TGF-β1) and vascular endothelial growth factor (VEGF) in renal tissue, and explore the effect and the action mechanism of erythropoietin (EPO) on renal interstitial fibrosis and the possible mechanism.MethodsA unilateral ureteral obstruction was used as the experiment model.722-3week-old SD rats were randomly divided into control group (A), UUO group (B) and UUO with treated group (C). Ureters of rats in group A were only separated, but not ligated. Rats in group C were administrated by rh-EPO(300IU/kg) three times a week. And the same volume of saline was administrated for the rats of group A and B. On days3rd,7th and14th after surgery,8mice in each group were sacrificed. Take the ipsilateral renal and observe its pathological changes by the ways of HE and Masson staining. The expression levels of a-smooth muscle actin (a-SMA), transforming growth factor-β1(TGF-β1) and vascular endothelial growth factor (VEGF) in renal tissue were detected by immunohistochemistry way. The collected experiment data were analyzed by statistics software SPSS17.0.Results(1)pathological changes:HE staining:There was no abnormal changes of rats renal tissue in group A in different time points; At3rd day, after the obstructive operation in group B, the renal tubules slightly expanded, and there were a small amount of mononuclear cells and lymphocyte infiltration; At7th day, these phenomenon was showed obviously. More tubules were dilated and atrophied occasionally, epithelial cells were denatured, oedematous, or even necrotic, and renal interstitial inflammatory cell infiltration was increased; At14th day, mesenchymal cells and extracellular matrix are much more, and the degree of interstitial fibrosis is more pronounced than before. In same time point, rat renal tissue in group C showed that the degree of tubular dilatation, monocyte and lymphocyte infiltration has declined compared with that in group B, and the degree of pathological changes is still more obvious than that in group A. Masson staining:There is no significant positive staining in rat renal tubules and interstitium in group A. With the time of obstruction going on, collagen fibers increased of rat renal in group B, the area of staining gradually also expanded. The degree of rat renal tubulointerstitial fibrosis significantly mitigated and the area of collagen fibers positive staining decreased in group C compared with that in group B(P<0.05), but its level is still higher than that in group A(P<0.05).(2) immunohistochemistry results:There is a small amount of expression of a-SMA and TGF-β1in renal tubules epithelial cells in group A. With the experiment time continuing, their expression levels were higher and higher and have reached to the maximum until14day in group B and group C. In same time point, the expression of these two proteins in group C were significantly reduced compared with those in group B (P<0.05), but still higher than those in group A (P<0.05); VEGF proteins were widely expressed in renal tubular epithelial cells and podocytes of group A. With the extension of the time of obstruction, the expression of VEGF was significantly lowered in group B and group C. But its expression was more obvious in group C than that in group B and was still lower than that in group A in same time point (P <0.05). In group A, the three proteins expression did not change significantly, the differences were not significant as well (P<0.05).ConclusionThe study shows that the increase of a-SMA and TGF-β1proteins expression and the decrease of VEGF protein expression play an important role in the procedure of renal interstitial fibrosis in young rats. In addition, intervention with EPO can ameliorate the tubulointerstitial fibrosis progress and protect the renal by downgrading the expression of a-SMA and TGF-β1and aggrandizing the expression of VEGF of rats with UUO. |
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