Effect Of Tanshinone ?A Combined With DAPT On The Expresssion Of NICD And Rbp-Jk Proteins In Renal Tissue Of UUO Model Rats

Objective: In order to provide scientific data for the compatibility of Chinese and Western molecular medicines of anti-renal fibrosis,analysis on the intervention effect of the compatibility of Tanshinone?A and DAPT on NICD,Rbp-Jk and other related proteins in renal tissue of rats with unilateral ureteral obstruction was performed.Methods:30 male SD rats were randomly divided into five groups,6 rats every group:normal group,model group,Tanshinone?A group,DAPT group,Tanshinone?A+DAPT group(compatibility group).All rats other than normal group was established UUO model.From the second day after operation,the normal group and the model group were given with CMC-Na,and the remaining treatment groups were given the corresponding drugs for2 weeks.The collagen deposition in renal tissue was observed by Masson staining.The expression of NICD and Hey1 in renal tissues were detected by immunohistochemical.The quantitative expression of Rbp-Jk and Col? was detected by Western blot method.Results: 1.Results of collagen fiber staining in kidney tissues of rats: In the normal group,a small amount of light blue collagen was seen in the renal capsule,showing a filamentous distribution;In the model group,a large amount of blue collagen was diffusely distributed in the renal stroma.The collagen deposition in each treatment group was significantly reduced compared with the model group(P<0.05).The scores of Masson in Tanshinone?A+DAPT group was significantly lower than that of Tanshinone?A and DAPT group(P<0.05).2.Expression of NICD and Hey1 protein in kidney tissues of rats in each group: The average optical density of NICD and Hey1 in the model group was significantly higher compared with the normal group(P<0.05).The average optical density of NICD and Hey1 of in each treatment group was significantly lower than that of the model group(P<0.05).Compared with the treatment groups,the average optical density of NICD and Hey1 in Tanshinone?A+DAPT group was significantly decline than that of Tanshinone?A group and DAPT group(P<0.05).The average optical density of NICD and Hey1 in the DAPT group was significantly lower than that of Tanshinone?A group(P<0.05).3.Relative expression of Rbp-Jk and Col?protein in kidney tissues of rats in each group:Compared with the normal group,the relative expression of Rbp-Jk and Col?protein in the model group increased significantly(P<0.05).The relative expressions of Rbp-Jk and Col? protein of each treatment group was significantly lower than that of the model group(P<0.05).Compared with the treatment groups,the relative expression of Rbp-Jk and Col?protein in Tanshinone?A+DAPT group was significantly decline than that of Tanshinone?A group and DAPT group(P<0.05).Tanshinone?A group had no significant difference in the relative expression of Rbp-Jk and Col?protein compared with DAPT group(P>0.05).Conclusion: Tanshinone?,DAPT and drug combination can improve the pathological damage of renal interstitial in UUO model,and reduce the collagen synthesis and deposition in the process of renal fibrosis.The mechanism may be related to inhibition of NICD,Rbp-Jk and Hey1 expression in renal tissue and effect the transduction of Notch/Jagged signaling pathway.