The Expression And Significance Of Bone Morphgenetic Protein-7(BMP-7) In Renal Tissue During Tubulointerstitial Lesion In Young Rat With Unilateral Ureteral Obstruction

Objective:To investigate the tendency of BMP-7 expression in the course of renal tubulointerstitial fibrosis with unilateral ureteral obstruction and the correlation of BMP-7 with tubulointerstitial damage,TGF-betal andα-SMA,and to evaluate the interfering effects with angiotensin converting enzyme inhibitor(ACEI) Benazepril and angiotensin-recepter blocks(ARB) Losartan.Methods:3 weeks young male Wistar rats(n=96) were randomly divided into sham-operated(control group),unilateral ureteral obstruction(model group) and Benazepril combined with Losartan treatment group(intervention group).UUO model was induced by ligating the left ureter of rats.Benazepril and losartan were separately administrated by gastric irrigation at 6mg/kg body wt every day after initial UUO and the other two groups were irrigated gastric with the same volume of vehicle in an identical manner.The eight rats were respectively sacrificed at 3,7,14 and 28 days.Pathological changes of the renal tissue were observed by HE and Masson staining,the protein expression of BMP-7,TGF-betal,α-SMA were detected by immunohistochemical staining.Results:After unilateral ureteral obstruction 3 day,mild renal interstitial edema,dilated tubule,tubulointerstitial with scattered inflammatory cell infiltration were observed,however the structure of glomerular is normal.Minor fibrosis was observed through Masson staining.With the progress of experiment,pathological changes in tubulointerstitial were becoming more and more serious.At 28th day,tubule were widely dilated,atrophied,degenerated and part of them were collapsed;abundant inflammatory cells infiltrated into renal tissue.Fibrosis were obviously observed by Masson staining.Compared with SOR group,there were difference significance in different time points(days 3,7,14,28).The extent of tubulointerstitial pathological changes in Benazepril combined with Losartan treatment group is more alleviative than the UUO group(P<0.05),but still more serious than the SOR group(P<0.05).Renal BMP-7 protein levels progressively decreased during the progression of obstructive nephropathy.Compared with the UUO group,the levels of BMP-7 protein were significantly increased in Benazepril combined with Losartan treatment group(P<0.05).The levels of TGF-β1 andα-SMA in UUO group were increased remarkably compared with the SOR(P<0.05).In Benazepril combined with Losartan treatment group,the levels of TGF-β1 andα-SMA were obviously decreased compared with model group(P<0.05).The renal tubulointerstitial expression of BMP-7 was significantly correlated with expression of TGF-β1(r=-0.844,p<0.01),α-SMA(r=-0.787,p<0.01) and tubulo interstitial injury index(r=-0.952,p<0.01)Conclusion:The decrease of BMP-7 and increase of TGF-β1 correlated with the increased expression ofα-SMA and the degree of interstitial lesions in obstructive nephropathy.This suggested that BMP-7 may block morphologic transformation of tubular epithelial cells,and TGF-β1 may induce EMT.Benazepril combined with Losartan treatment suppress fibrosis,at least in part via down-regulating TGF-β1,α-SMA expression and up-regulating BMP-7 expression in the affected kidney,and exhibit a remarkable ability to block this epithelial to myofibroblast transition in vivo.From our results,BMP-7 may be taken into consideration as a therapeutic agent for the prevention and treatment of chronic renal diseases.