Regulation of renal cortex p21 CIP1 protein expression by benazepril and its mechanism in diabetic rats

Objective To investigate the regulation of renal cortex p21 CIP1 protein expression by benazapril and its mechanism in diabetic rats. Methods The rats were randomly divided into following groups: uninephrectomized rats, streptozotocin induced diabetic rats and diabetic rats treated with benazepril (10mg·kg -1 ·d -1 , by gavage). Angiotensin converting enzyme (ACE) activities were determined by fluorimetric assay in plasma and renal cortex and medulla. Renal cortex transforming growth factor β1 (TGFβ1) mRNA expression was assessed by Northern blot analysis, and TGFβ1 and p21 CIP1 protein expression was measured by Western blot analysis. Results After 1 week, diabetic rats developed a body weight loss, an increased kidney weight/body weight and an elevated ACE activity in renal cortex despite a decreased ACE activity in plasma. Northernblotanalysisshowedthatrenal cortex TGFβ1 mRNAexpressionindiabeticrats increased by 63.6%, as against uninephrectomized rats. Western blot analysis noted that TGFβ1 and p21 CIP1 protein expression was also increased. Administration of benazepril for one week could significantly suppress kidney hypertrophy and ACE activities were reduced by 89.0%, 70.0% and 70.5% in plasma and renal cortex and medulla, respectively. Expressions of TGFβ1 mRNA, TGFβ1 and p21 CIP1 protein were decreased by 47.7%, 49.5% and 60.0%, respectively. Conclusion Benazepril may suppress increased p21 CIP1 protein expression in diabetic rats and its mechanism may partially be related to down regulation of TGFβ1 expression.