Effect And Mechanism Of Renal Progenitor Cells Induced By Erythropoietin On Ischemia-reperfusion Injury After Nephron Sparing Surgery

Background: NSS was a new surgery methods for renal cell carcinoma(RCC)which enucleation of the tumor tissue while preserve the normal renal tissues.NSS can also preserve renal function and prevention of end-stage renal failure even uremia,and improve the quality of patients life.The IRI during the surgery is the main cause and need to be solved urgely.Research confirmed that endogenous stem cell-RPCs were in a dormant state under normal physiological conditions,and RPCs can rapidly differentiate into renal tubular epithelial cells participate in the repair of renal IRI when renal IRI was occurred.In recent years,EPO has been confirmed had protective effect under renal and cardiovascular IRI,however,it is not clear whether EPO can mobilize RPC to protect IRI in NSS.Objective:To investigate the effects of the EPO on IRI in rats with NSS and the potential mechanism,in order to provide new evidence for clinical application.Materials and methods: Fifty-four Sprague-Dawley rats were divided into three groups randomly: Sham group,NSS group(PBS+NSS)and(3)EPO group(EPO+NSS).During NSS,renal artery was clamped for 40 min induce IRI.Sham group just adopted exposure renal artery without vascular clamped.Rats in NSS group were injected intraperitoneally with PBS for 3 days before NSS.Rats in EPO group were injected intraperitoneally with EPO for 3 days before NSS.After 12 h,24h,72 h,blood sample and renal tissues were collected.The serum creatinine(Scr)and urea nitrogen(BUN)were evaluated.The pathology injury was evaluated by HE staining.The CD24/CD133 double-positived RPCs were tested by flow cytometry.The CD133 and PCNA protein were quantified by immunohistochemical staining.The expressions of Wnt7 b and ?-catenin protein were detected by Western blotting.Results: Compared with those in the Sham group,the Scr and BUN in the NSS group were significantly increased in any time after the surgery(P<0.05),the same to the pathology injury score.Compared with those in the NSS group,the Scr and Bun in the EPO group were significantly lower 24 h after the surgery(P<0.05),and the pathology injury score also decreased(P<0.05).The proportion of the RPCs,expressions of CD133 and PCNA,Wnt7 b and ?-catenin protein were significantly higher after 24 h of the surgery in EPO group than those in the NSS group..Conclusions: EPO may reduce renal IRI induced by NSS;RPCs could be mobilized by EPO preconditioning,and its mechanism may be related to the Wnt7b/?-catenin signal pathway.