Objective:Diabetic nephropathy (DN) is one of the most common causes of end-stage renal failure.The pathogenesis of progressive renal injury is multifactorial and the mechanism by which hyperglycemia causes microangiopathy is still poorly understood.The WNT pathway is activated in DN and regulating β-catenin protein levels is referred to as the canonical Wnt/β-catenin pathway.Because the renin angiotensin system has been reported to be an important contributory factor in the pathophysiology of DN,exogenous administration of angiotensin Ⅱ receptor antagonist may be beneficial in counteracting some biochemical or functional changes of DN.The aim of the study was to determine the β-catenin expression and the possible protective effects of irbesartan,an angiotensin Ⅱ type 1 receptor blocker (ARB) in a rat model of streptozotocin(STZ)-induced diabetic nephropathy.Methods:STZ-induced DN in rats was assessed biochemically by measuring urine volume,protein and creatinine clearance as well as Kidney weight/body weight (KW/BW) and the index of mesangial expansion.Three groups of male Sprague-dawley rats were used.The first group consisted of non-diabetic control rats (control).The second group was the untreated diabetic rats(STZ+vehicle).The third group consisted of diabeti rats treated with irbesartan,50 mg/kg for 12 weeks (STZ+irbesartan).Immunohistochemical stainings and real time PCR for β-catenin were performed in renal cortex of rat modals.Results:Marked hyperglycemia,polyuria,proteinuria,renal hypertrophy,mesangial matrix expansion and glomerular hyperfiltration were observed in STZ diabetic rats.The levels of microalbuminuria and KW/BW in the STZ+irbesartan group were lower than those in the STZ+vehicle group (P＜0.05).The up-regulated immunostaining and mRNA expression of β-catenin were decreased in renal cortic of the Irbesartan-treated diabetic group,but there was no significant difference compared to the untreated diabetic group.Conclusion:The data suggest that irbesartan ameliorates proteinuria and renal hypertrophy,charactered damages of STZ-induced early-stage DN in rats,but its effective drug target is not to inhibit the up-regulated expressions ofβ-catenin.