Effect Of Tanshinone ⅡA Combined With DAPT On The Expresssion Of Wnt1 And β-catenin Proteins In Renal Tissue Of UUO Model Rats

Objective:To study the effect of tanshinone Ⅱ A and DAPT on the expression of Wnt1 and β-catenin protein in renal tissue of UUO rats.To find the possible the curative effect mechanism of tanshinoneⅡA combination with DAPT,and provide experimental basis for the clinical application.Methods:40 male SD rats were randomly divided into 5 groups and named as sham operation group,model group,tanshinoneⅡA group,γ-secretase inhibitor(DAPT)group and tanshinoneⅡA compatible DAPT group(referred to as tanshinoneⅡA+DAPT group).They were given corresponding drug intervention for 14 days after modeling.We will observe the renal pathology by Masson staining.The expression of Wnt1 and MMP7 protein was detected by immunohistochemical(IHC)method.Western blot(WB)was used to detect the expression of Wnt1,β-catenin and Numb protein.Results:1.Pathological results of Masson staining:A small amount of blue collagen deposition was observed in the renal interstitium of the sham operation group.In the model group,large amounts of blue collagen were widely deposited in the rat renal interstitium,and the masson score of renal tissue in the model group was significantly higher than that in the sham group(P <0.05).Compared with the model group,all the drug intervention group with the blue collagen deposition in the renal tissues of rats have reduced and the Masson score were significantly decreased(P <0.05).The effect of the tanshinone IIA+DAPT group was obvious(P <0.05).2.Results of immunohistochemical detection: Compared with the sham operation group,Wnt1 and MMP7 proteins were widely expressed in renal tubules and interstitium in the model group,and the mean optical density values of Wnt1 and MMP7 in the renal tissue of the model group were significantly increased(P <0.05);compared with the model group,the expression of Wnt1 and MMP7 proteins in renal tubules and interstitium were decreased in the drug intervention group,and the mean optical density of Wnt1 and MMP7 in the drug intervention group the values were significantly decreased(P <0.05);The comparison between administration groups,the effect of the tanshinoneⅡA + DAPT group was the most significant(P <0.05).3.Western blot detection results showd that: Compared with the sham operation group,the relative expression of Wnt1,β-catenin and numb proteins in the renal tissue of the model group was significantly increased(P<0.05);Compared with the model group,the expression level of Wnt1,β-catenin and numb proteins in the renal tissues of each medication intervention group was significantly reduced(P <0.05).The relative expression of Wnt1,β-catenin and numb proteins in the kidney tissue of tanshinone IIA+DAPT group was significantly lower than thetanshinone IIA group and DAPT group(P <0.05).Conclusion:Tanshinone IIA,DAPT and their compatible drugs could reduce UUO rats renal tissue damage.This phenomenon may be related to its decreased expression of the Wnt1,β-catenin,MMP7 and Numb proteins in renal tissues of UUO model rats and delay the progression of renal fibrosis.