The Protective Effect Of Irbesartan On Renal Tubulointerstitial Fibrosis With Unilateral Ureteral Obstruction In Rats

objective To investigate the impact of Irbesartan on MMP-9, TIMP-1mRNA in experimental renal interstitial fibrosis,explore if have Irbesartan protective effect on rats with renal interstitial fibrosis and its mechanism .methods 48Wistar rats were used,weight 160-180g, which were divided randomly into three groups of 16rats:Sham, UUO, Irb.unilateral ureteral obstruction were used by ligating the left uretera,the sham group take the seem opration except for not ligating the left uretera.Four rats from each groups were sacrificed at 3, 10, 20, 30days after UUO.24-hour urine volume was collected .left kidney of each rats was stained with hematoxylind eosin method. Evaluate the degree of tubular-interstitial damage.a-smooth muscle actin(α-SMA) were identified using an immunohistochemistry technique.matrix metalloproteinase-9 and its main inhibitor tissue inhibitor of metalloproteinase-1 mRNA was analyzed by reverse transcription-PCR(RT-PCR).The relation between TIMP-lmRNA and renal interstitial damage index ,a-SMA in the rats were examined.Results The difference of 24-hour urine protein volume has no statistically significant(p>0.05).In UUO group, the tubulointerstitial damage index , α-SMA ,and TIMP-1 mRNA were significant decreased compared with Sham (p<0.01),but those indicates decreased in Irb (p<0.01, p<0.05). The expression of MMP-9 mRNA was increased compared with Sham in UUO,it reaches its peak at ten days then begin to decrease from that.In Irb,MMP-9 level was higher than that in UUO from 20 days(p<0.01).The TIMP-lmRNA was positively correlatedremarkably with the tubulointerstitial damage index, a-SMA, (r=0.92,0.94, P<0.001).
conclusions (D 24-hour urine protein volume has no statistical variance after UUO in rats.(2)The banlane of MMP-9/TIMP-1 play an important role in the progression of renal interstitial fibrosis with unilateral ureteral obstruction.Irb regulates the expression of MMP-9/TIMP-1,which may promote matrix degradation , attenuate progression of renal interstitial fibrosis .