A Proteomics Study On The Effect Of Zhenwujiawei Decoction On Rats With Renal Interstitial Fibrosis

Objective:The purpose of this study is to investigate the effete of Zhenwujiawei decoction on the changes of renal histomorphology and fuction in unilateral ureteral obstruction rats, and based on the method of proteomics to illustrate the mechanism of the Zhenwujiawei decoction on delaying renal interstitial fibrosis.Method:The 200 male wistar rats were randomly divided into five groups:normal group, sham operation group. UUO group, Zhenwujiawei decoction group, fosinopril group, each group had 40 rats. The rats were given daily intragastric administration from the first day after UUO surgery as following, the Zhenwujiawei decoction group given with Zhenwujiawei decoction, the fosinopril group given with fosinopril solution,the rest groups given with distilled water. Ten rats were randomly chosen to put into the metabolism cage at 6th> 13th、20th、27th day after the UUO surgery and then executed the next day. The 24 hour urine, blood serum and obstructed kidney were collected and tested.Results:(1) The weight and urine volume were higher in Zhenwujiawei decoction group than the UUO group at each time point (P<0.05)(2) The Scr, BUN and the quantitate of 24h urinary protein were lower in Zhenwujiawei decoction grouop than UUO group at each time point (P<0.05)(3) The pathological change and fibrosis area were lower in Zhenwujiawei decoction group than UUO group at each time point (P <0.05)(4) The distince protein between Zhenwujiawei decoction and UUO group was identified 404 protein, when the whole protein number was 6763; and there was 245 protein up-regulation and 159 protein down-regulation in Zhenwujiawei decoction group.(5) Bioinformatics analysis indicated that the Zhenwujiawei decoction may involve a lot of signaling pathway and cytokines such as PI3K-Akt、PPAR、HIF-1、MAPK、Notch、TNF, and so on.Conclusion:(1) The Zhenwujiawei decoction can reduce the level of Scr,BUN and proteinuria to protect the function of kidney in UUO rats.(2) The Zhenwujiawei decoction can alleviate the pathological change and the fibrosis area of kidney in UUO rats.(3) 404 protein were discovered to be the anti-fibrosis target therapy protein of Zhenwujiawei decoction, of which 245 were up-regulation and 159 were down-regulation.(4) The mechanism of Zhenwujiawei decoction alleviating the RIF may involve impacting a lot of signaling pathway such as PI3K-Akt,PPAR,HIF-1,MAPK,Notch and TNF,etc.(5) The distinct protein such as Aurora kinase,AHNAK and Coronin has not been reported to be related with RIF.