Expression Of VEGF And FN In The Renal Tubule-inierstitium Of Aristolochic Acid Nephropathy Model And The Function Of Prednisone In Preventing And Therapying Fibrosis

Objectives1.To establish a rat model with Aristolochia manshuriensis Kom and observe the changes of kidney tissue histology.2.To detect the kinetic expression of vascular endothelial growth factor(VEGF),hypoxia inducible factor-1α(HIF-1α),and fibronectin(FN) in the renal tubule-interstitium of rats with Chronic aristolochic acid nephrology and to discuss their influence on the renal interstitial fibrosis of CAAN rats.3.To illustrate the effect of prednisone on the fibrosis of aristolochic acid nephropathy in rat model.Methods1.Forty-six male Wistar rats were divided randomly into two groups: experimental group(n =34,among the total 24 rats were killed asmodel group and others were killed as prednisone group),first perfused intragastrically with decoction of Caulis aristolochiae manchuriensis Kom for 12 weeks,and control group(n =12,perfused intragastrically with tap water for 12 weeks).At the ends of 4,8,12 and 16 weeks,6 rats in model group and 3 rats in control group were killed.10 rats in prednisone group were killed at the end of 16 weeks.Specimens of renal tissues were collected before the killing of the rats for further test.2.HE and Masson staining and microscopy were used to observe the histology of renal tissues.The relative area of renal interstitium was detected to evaluate the degree of renal interstitial fibrosis.Immunohistochemistry were used to detect the expression of HIF-1α,VEGF and FN.3.Statistical software SPSS13.0 was used for statistical treatment.Measurement datas were represented as(?)±s.T-test was used for interclass difference test. Pearson correlation analysis was used for correlation test.Results1.No pathology changes were found in control group.In control group, tubulointerstitial lesions became more and more serious in model group,at the end of 16 weeks all rats developed renal hypocellular interstitial fibrosis.The relative area of renal interstitium increased significantly(P＜0.01) in the model group compared to that in control group.Compared with model groups,the optical density of FN was significantly lower in prednisone group(P＜0.05,)2.In control group,VEGF expressed in renal tubule-interstitium.But HIF-1αand FN slightly or scarcely expressed in renal tubule-interstitium.In model group the expression of VEGF came to peak at the end of 8 weeks,and then gradually decreased;the expression of HIF-1αand FN(P＜0.01) gradually increased.At the end of 16 weeks,the expression of VEGF in specimens of renal tissues from prednisone group was significantly higher than that from model group.but the expression of HIF-1αand FN were significantly lower.3.Correlation analysis:In model group,there were significantly positive correlations among the HIF-1α,FN expression and the relative area of renal interstitium(HIF-1αvs FN r=0.0.958,HIF-1αvs the relative area of renal interstitium r=0.0.971,FN vs the relative area of renal interstitium r=0.0.961,P＜0.01).Conclusions1.In CAAN rats,there is intimate relation between the change of VEGF made by change of HIF—1αand the renal interstitial fibrosis of rats with CAAN.FN is more important during the period of renal interstitial fibrosis progression.2.Prednisone can alleviate the fibrosis of aristolochic acid nephropathy rats.