The Expression And Significance Of Hypoxia Inducible Factor-1α At Fibrotic Tubulointerstitium In Kidney From UUO Young Rats

ObjectiveTo observe the trend,relevance and potential pothgentic significance of hypoxia inducible factor-1 a (HIF-1α)and transforming growth factor-β1(TGF-β1) in the course of tubulointerstitial lesions in kidneys of young rats with unilateral ureteral obstraction (UUO), and the interfering effects of the treatment with benazepril and losartan.MethodsYoung male wistar rats by unilateral ureteral obstruction(UUO) were served as experiment models. All of the rats were randomly divided into three groups,that was untreated group after UUO(UUO group,n=24),treated group after UUO(UUO+ACEI+ARB group,n=24),and sham operation group(control group,n=24).At the time points that treated for 3,7,14,28 days, six rats were sacrificed in each group and the left renal tissues were obtained to evaluate the renal tissues morphologic changes through Masson staining,,at the same time we detected the protein expression of HIF-la and TGF-β1 in tubulointerstitial by immunohistochemical ways.Finally,we evaluated the correlation among HIF-la and TGF-β1 protein expression in localization and time phase..All the data of experiment were analyzed by statistics software SPSS13.0.Results(1)Morphological changes:At day 3,dilated tubule,infiltrated into renal tissues of slight inflammatory cells,and swelling of tubular epithelial cells were observed in untreated group after UUO. It was showed obviously at day 14,such as,more tubule were dilated;generous inflammatory cells infiltrated into renal tissue,especially in tubulointerstitial regions;cellulose exudation and tubulointerstitial area broaden. With the experimental session continuing,pathological changes in tubulointerstitial were becoming more and more serious in untreated group after UUO.Compared with control group,there were difference significance in different time points(days 3,7,14 and 28).The extent of tubulointerstitial pathological changes in treated group after UUO is more alleviative than the UUO group(P<0.01),but still more serious than the control group(P<0.01). (2)Expression of HIF-la and TGF-β1 proteins:①Immunohistochemical staining indicated that HIF-la and TGF-β1 proteins were expressed slightly in tubule epithelial cellular of control group,and almost no exist in tubulointerstitial regions and glomerular. There was no difference in all the time points(P>0.05).②Compared with control group,the level of expression of the four proteins were increased gradually,in tubule, tubulointerstitial regions and tubule epithelial cellular,the expression of TGF-β1 proteins peaked at day 14,and a slight decrease was observed at day 28, Obviously higher than the control group.③The tendency of those factors'expression was inhibited in each treated group(P<0.01),but still higher than control group(P<0.05).The significant difference were observed between treated and untreated groups in different time points(P<0.01). (3)Correlation analysis:Positive correlations were observed among the observived factors(P<0.01)ConclusionIn the course of tubulointerstitial lesions with young rats, the up-regulated expression of HIF-la and TGF-β1 exhibit a great malgenic sense, while the benazepril and losartan treatment have a visible interfering effects.