Effect Of Regulating Collateral And Eliminating Turbidity Liquid On The Gene Expression Of Matrix Metalloproteinase-9(MMP-9) And Tissue Inhibitor Of Metalloproteinases-1(TIMP-1) In Renal Interstitial Fibrosis In Rats

objective To explore the changes of gene expression of metalloproteinase-9(MMP-9) and tissue type inhibitors of metalloproteinase-1(TIMP-1) and elucidate the role of imbalance betw -een MMP-9 and its major inhibitor TIMP-1 in the renal interstitial fibrosis with unilateral ureteral obstruction, investigate the mechanisms of renal interstitial fibrosis and the preventive and theraputic effects of Regulating Collateral and Eliminating Turbidity Liquid(REL) on renal interstitial fibrosis.Methods Unilateral ureteral obstruction(UUO) rat animal models by ligating the left ureter were used.48 Wistar rats were randomly divided into 3 Groups of 16rats: Sham-oparation ,UUO and UUO+REL.Four rats from each groups were sacrificed at 3, 10, 20, 30days after UUO. 24-hour urine volume was collected ,serum creatinine and urea nitrogen levels were measured. Left kidney of each rats was stained with hematoxylind eosin method. Evaluate the degree of tubular-interstitial damage. α -smooth muscle actin ( α -SMA)and collgen type Ⅳ 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-1mRNA and renal interstitial damage index , α -SMA , collgen type Ⅳ in the rats were examined.Results The difference of 24-hour urine protein volume has no statistically significant (p>0.05),also within the Scr, BUN at the time point three day.But In UUO rats,the levels of Scr,BUN were increased compared with sham group(p<0.01) from the ten days. The group of UUO+REL was decreased compared with UUO(p<0.01).In UUO group, the tubulointerstitial damage index , a -SMA , collgen type IV and TIMP-1 mRNA were significant decreased compared with Sham (p<0.01), but those indicates decreased in UUO+REL(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 UUO+REL, MMP-9 level was higher than that in UUO from 20 days(p<0.01). The TIMP-lmRNA was positively correlated remarkably with the tubulointerstitial damage index , a -SMA, collgen type IV(r=0.92 , 0.94, 0.95 P< 0.001).conclusions (D 24-hour urine protein volume has no statistical variance after UUO in rats. ?The Sa\ BUN levels are obviously increased after UUO in rats, the renal interstitial fibrosis is one of the most important causes leading to the impairment of renal function.@The banlane of MMP-9A1MP-1 play an important role in the progression of renal interstitial fibrosis with unilateral ureteral obstruction.?REL regulates the expression of MMP-9/TIMP-l,which may promote matrix degradation , attenuate progression of renal interstitial fibrosis and retard the impairment of renal function.Postgraduate hai-jun Iiu (Nephrology)Directed by li-qiu Iiu Professorjun-sheng yu Professor...