Chymase inhibition protects diabetic rats from renal lesions

The present study aimed to investigate the effects of a chymase inhibitor on renal injury in diabetic rats. A total of 24 Sprague-Dawley rats were randomly divided into the following groups: The control group (n=7), the diabetes group (DM group; n=7), and the DM + chymase inhibitor group (DM + Chy-I group; n=10). Diabetes was induced via an intraperitoneal injection of streptozotocin (65 mg/kg). Rats in the DM + Chy-I group were administered 1 mg/kg chymase inhibitor [Suc-Val-Pro-Phe(P)-(OPh)(2)] daily for 12 weeks by intraperitoneal injection. Subsequently, kidney weight, various biochemical parameters and blood pressure were measured. In addition, the expression levels of fibronectin (FN), type IV collagen (ColIV), transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) were determined by immunohistochemistry and reverse transcription polymerase chain reaction. Compared with in the DM group, the levels of serum cholesterol and urinary albumin/creatinine were decreased in the DM + Chy-I group (P<0.05). Furthermore, chymase inhibition reduced the overexpression of FN, ColIV, TGF-β1 and VEGF (P<0.05) in the renal tissue of diabetic rats. These results indicated that chymase inhibition may reduce the excretion of urinary albumin and the deposition of extracellular matrix components in the kidney of diabetic rats. These effects may be mediated by altered expression of the VEGF and TGF-β1 pathways. In conclusion, chymase inhibition may be considered a potential method for the treatment of renal damage.