Abstract: Objective To develop a rat model of type 2 diabetic nephropathy and to investigate changes in tubular-interstitial pathomorphology and expression of TGF-β1,HGF and CTGF in early-stage diabetic nephropathy.Methods Forty-four eight-week-old male Wistar rats were fed a normal or high-energy(46% of total calories from fat) diet for 20 weeks,and at week 6 rats received once intraperitoneal injection of citric acid buffer or STZ(30 mg/kg).In the eighth week,two groups underwent intraperitoneal injection glucose tolerance test(IPGTT).Body weight,fasting blood glucose,insulin,24 hour urine albumin excretion and creatinine clearance rate were monitored after the feeding programme.The tubular structural changes were examined with HE staining and periodic acid-silver methenamine staining at week 14 and week 20.The protein expression of TGF-β1,HGF and CTGF in tubular-interstitial were determined by immunohistochemistry at week 14 and week 20.Results 1) The rats fed high-energy markedly showed obesity,hyperglycaemia,hyperinsulinemia,insulin resistance and albuminuria.2) There were severe structural alterations of hepatic tissue,pancreas and tubular-interstitium in rats fed high-energy diet.3) The protein expression of TGF-β1 and HGF increased significantly in rats fed high-fat(P<0.05),while CTGF had no significantly changed.Conclusion 1) Tubular-interstitial pathomorphology in the rats of the early-stage diabetic nephropathy have been fibrosis.2) The protein expression of TGF-β1,HGF and CTGF in tubular-interstitium are unbalanced,which may be associated with diabetic nephropathy progression.

Key words: type 2 diabetic nephropathy, tubular-interstitial, transforming growth factor, hepatocyte growth factor, connective tissue growth factor