Expression Of CTGF And HIF-1a In The Renal Tubule-Interstitium Of Rats With Chronic Aristolochic Acid Nephrology

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 transforming growth factor-β1(TGF-β1), connective tissue growth factor(CTGF),hypoxia inducible factor-1α(HIF-1α), vascular endothelial growth factor(VEGF)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.Methods1.Thirty-six male Wistar rats were divided randomly into two groups:model group(n=24 perfused intragastrically with decoction of Caulis aristolochiae manchuriensis Kom for 12 weeks)and control group(n=12,perfused intragastrically with tap water for12 weeks).At the ends of 4,8,12 and 16 weeks, 6 rats in model group and 3 rats in control group were killed.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 TGF-β1,CTGF,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.2.In control group TGF-β1,CTGF,HIF-1αand FN slightly or scarcely expressed in renal tubule-interstitium.VEGF extensively expressed in renal tubule-interstitium.In model group the expression of TGF-β1 came to peak at the end of 8 weeks,and then gradually decreased;the expression of CTGF,HIF-1αand FN(P＜0.01)gradually increased.No changes were found of VEGF.3.Correlation analysis:In model group,there were significantly positive correlations among the CTGF,HIF-1α,VEGF,FN expression and the relative area of renal interstitium(CTGF vs HIF-1αr=0.980,CTGF vs FN r=0.963,CTGF vs the relative area of renal interstitium r=0.966,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).ConclusionsDuring the period of renal interstitial fibrosis,TGF-β1 primarily participated in the initiating period;CTGF and HIF-1αparticipate in the whole period,they are more direct and important with renal interstitial fibrosis.