关键词: 转化生长因子β, 糖尿病肾病, 纤连蛋白类, 胶原Ⅳ型

Abstract: To investigate the dynamic expressions of urotensinⅡ (UⅡ) and transforming growth factor-β1 (TGF-β1) in renal tubular epithelial cells and glomeruli of diabetic rats and their roles in pathogenesis of diabetic nephropathy (DN). Methods Thirty male Wistar rats were randomly divided into normal control,2-week (2-wk DM),4-week (4-wk DM),8-week (8-wk DM) and 12-week (12-wk DM) diabetic groups.Diabetic model was induced by a single intraperitoneal injection of streptozotocin (55 mg•kg^-1).Blood glucose (BG),serum and urinary creatinine,urinary albumin (UAlb) and urinary N-acetyl-B-D-glucosaminidase (NAG) contents were dertemined with biochemical methods.Immunohistochemistry was used to detect the expressions of UⅡ,TGF-β1,fibronectin (FN) and collagenⅣ (Col Ⅳ) in the kidney. Results BG,creatinine clearance (Ccr),UAlb and NAG levels were significantly elevated in diabetic groups (P<0.05).As compared with control,positive staining of UⅡ and TGF-β1 was observed in the renal tubular epithelial cells and glomeruli of diabetic rats.Progressively increased UⅡ and TGF-β1 expressions were found in 4-,8- and 12-wk DM groups (P<0.05) with diabetic course compared with 2-wk DM.The expression of UⅡ protein in the renal tubular epithelial cells was positively correlated with urinary NAG content (r=0.895，P<0.01).The expression level of UⅡ in the renal tubular epithelial cells was positively correlated with that of TGF-β1 (r=0.769，P<0.01).The expressions of FN and Col Ⅳ in diabetic kidney in 8- and 12-wk DM groups were obviously increased compared with normal control (P<0.05).Conclusion The expressions of UⅡand TGF-β1 proteins are markedly increased in the renal tubular epithelial cells and glomeruli of diabetic rats,suggesting that UⅡand TGF-β1 may play roles in the renal tubular lesion and extracellular matrix accumulation of diabetic nephropathy.

Key words: transforming growth factor-beta, diabetic nephropathy, fibronectins, collagen type Ⅳ