RESUMO
AIM: To investigate the influence of irbesartan (Irb), a new angiotensin II receptor 1 antagonist, on renal hypertrophy in streptozotocin (STZ)-induced diabetic rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: normal group (Group N, n=7), diabetic group (Group DN, n=6) and irbesartan treated group (Group DNI, n=7). In the experimental group, after the rats subjected to uninephrectomy, STZ was given by peritoneally injection at bolus dose of 50 mg/kg to induce diabetes. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), 24 hour proteinuria (24 h Upro) were measured at week 4, 8, 12, respectively. By the end of experiment at week 12, creatinine clearance (Ccr), kidney weight (KW), indicator of renal hypertrophy (KW/BW), renal total protein content (RTP), glomerular area (AG) and glomerular volume (VG) as well as glomerular basement membrane (GBM) were determined by semi-quantitative pathology technique. RESULTS: It was showed that there was no significant difference in BG between group DN and DNI, while Irb significantly reduced the increasing of Ualb, 24 h Upro in diabetic rats compared to control group (P
RESUMO
AIM To explore the effect of ACE inhibitor on early kidney hypertrophy and its mechanism in diabetic rats. METHODS Rats were randomly divided into three groups: uninephrectomized rats, streptozotocin induced diabetic rats and diabetic rats treated with benazepril (an ACE inhibitor, 10 mg?kg -1 ?d -1 , ig). Activity of ACE was determined by the fluorimetric assay. Expression of TGF? 1 mRNA and TGF? 1 and p21 CIP1 protein was measured by Northern blot analysis and Western blot analysis, respectively. RESULTS After 1 week, the diabetic rats developed a body weight loss, kidney weight/body weight increased and renal cortex ACE activity elevated despite a decrease in plasma ACE activity. Northern blot analysis showed that renal cortex TGF? 1 mRNA expression in the diabetic rats was enhanced by 1.3 times, compared with uninephrectomized rats. Western blot analysis showed that TGF? 1 and p21 CIP1 protein expression were also increased. Administration of benazepril for one week significantly suppressed kidney hypertrophy. ACE activity in the plasma, renal cortex and medulla was reduced by 89%,70% and 70 5%, respectively. Expression of TGF? 1 mRNA as well as expression of TGF? 1 and p21 CIP1 protein was reduced by 47 7%, 49 5% and 60 0%, respectively. CONCLUSION Our results suggest that the suppression of ACE inhibitor on diabetic kidney hypertrophy might partially be associated with a decrease in the expression of TGF? 1 and p21 CIP1 in diabetic rats renal cortex. However, its exact mechanism remains to be further explored.