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.
Ren
Xiaojun
X
Department of Internal Medicine of Renal Disease, Second Hospital of Shandong University, Shandong, China.
Guan
Guangju
G
Liu
Gang
G
Liu
Gaohong
G
D000199:Actins / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism*; D000077405:Irbesartan; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009395:Nephritis, Interstitial / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D055513:Connective Tissue Growth Factor; D003404:Creatinine; D000077405:Irbesartan; D012709:Serum Albumin; D013777:Tetrazoles; C498862:Acta2 protein, rat