Irbesartan ameliorates diabetic nephropathy by reducing the expression of connective tissue growth factor and alpha-smooth-muscle actin in the tubulointerstitium of diabetic rats.

The effect of irbesartan on the expression of connective tissue growth factor (CTGF) and alpha-smooth-muscle actin (alpha-SMA) in the renal tubulointerstitium of diabetic rats was investigated in our study. Diabetes was induced in male Wistar rats by intraperitoneal administration of streptozotocin (STZ), 60 mg.kg(-1) body weight. The rats were then randomized to a diabetic group (DM) and an irbesartan therapy group (DM + Irb). The normal group (non-DM) rats were administered only citrate buffer. At the end of the 16th week, blood glucose, kidney weight/body weight, urine albumin (UAlb) and creatinine clearance rate were determined. The renal histopathology was observed by light microscopy. Further biochemical analysis of CTGF and alpha-SMA was provided using real-time reverse transcription PCR, immunostaining and Western blotting techniques. Compared with the non-DM group, blood glucose, kidney weight/body weight, UAlb, creatinine clearance and interstitial fibrotic lesions were increased in the DM group (p < 0.01). Treatment with irbesartan improved these parameters except blood glucose. Compared with the non-DM group, expressions of CTGF and alpha-SMA in the renal tubulointerstitium were highly upregulated in the DM group (p < 0.01). Administration of irbesartan prevented the high expressions of CTGF and alpha-SMA in renal tissue of diabetic rats. These results indicated that irbesartan can protect the kidney of STZ-diabetic rats by reducing the expression of CTGF and alpha-SMA in the renal tubulointerstitium. 2008 S. Karger AG, Basel.