Effects Of Tanshinone ?A Combined With DAPT On The Expression Of NICD,Hes-1 And E-cadherin In Renal Tissue Of UUO Rats

Objective: To observe the effect of Tanshinone ? A(TS ? A)combined with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester(DAPT)on the expression of Notch intracellar domain(NICD),Hairy enhancer of split-1(Hes-1)and Epithelial cadherin(E-cadherin)in renal tissue of unilateral ureteral obstruction(UUO)rats,providing a new basis for the combined application of Chinese and Western medicines into the clinic.Methods: Thirty male SPF SD rats were randomly divided into five groups,6 per group: normal group,model group,Tanshinone ?A group,DAPT group,Tanshinone ?A+ DAPT group.In addition to the normal group,the right ureter was ligated in each group,resulting in UUO model.The normal group and model group were treated with 0.5%CMC-Na,the rest of the treatment groups to the corresponding drug gavage for 14 days.The pathological changes of renal tissue were observed under light microscope.And the expression of NICD in rat kidney was detected by immunofluorescence method anddetected Hes-1 and E-cadherin in rat renal tissue by immunohistochemistry.Results: 1.HE staining results In the normal group,no pathological damage was found in the kidney of rats.A large amount of atrophy,renal tubular atrophy or expansion of renal tubular epithelial cells were seen in the kidney of UUO rats.And renal interstitial fibrosis was obviously.Compared with the model group,the other groups HE scores were significantly lower(P?0.05),while the scores of HE in tanshinone ?A group and DAPT group were lower in each treatment group(P ?0.05).2.NICD immunofluorescence test results Fluorescence microscopy shows: NICD protein was red fluorescence,the expression is located in the cytoplasm of renal tubular epithelial cells.The fluorescence of cytoplasm of renal tubular epithelial cells in normal renal tissue was weak(±),while in model renal tissue was significantly increased(+++).Compared with the model group,though NICD fluorescence in tanshinone ? A group,DAPT group and combined group was significantly weakened,in which combined groupdecreased more significantly(±),followed by DAPT group(+),and tanshinone ? A group slight decrease compared with the model group fluorescence(+ +).3.Hes-1 immunohistochemistry test results Compared with the normal group,the Hes-1 average optical density of model group and tanshinone?A group was significantly increased(P?0.05),indicating that Hes-1 was obviously deposited in renal tissue of UUO rats.The mean optical density of Hes-1 in all groups was significantly lower than that of the model group(P ?0.05),indicating that tanshinone ? A combined with DAPT can effectively reduce the expression of Hes-1 in renal tissue of UUO rats,while there was no significant difference between the other groups(P?0.05).4.E-cadherin immunohistochemistry test results The average optical density of E-cadherin in the model group was significantly lower than that in the normal group(P?0.05),indicating that the positive expression of E-cadherin in the UUO rats decreased significantly.Compared with the model group,the mean optical density of E-cadherin in treatment groups was significantly increased(P?0.05).Compared with Tanshinone?A +DAPT group,the average optical density of E-cadherin in Tanshinone ? A and DAPT groups decreased(P?0.05),indicating that tanshinone ? A combined with DAPT could effectively increase the expression of E-cadherin in UUO rats.There was no significant difference between Tanshinone?A and DAPT groups(P?0.05).Conclusion: Tanshinone?A combined with DAPT can improve renal pathological injury of UUO rats in a certain degree,delay the progression of chronic kidney disease and it can protect the kidneys.Mechanism may be related to reducing the deposition of NICD,Hes-1 in renal tissues and promoting the expression of E-cadherin in kidney tissue.