AIM: To investigate the mechanisms of angiotensin II receptor antagonist irbesartan (Irb) in prevention of renal lesion in streptozotocin (STZ)-induced diabetic rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: normal control (group N), diabetic nephropathy (group DN), and diabetic nephropathy treated with Irb (group DNI). Diabetes was induced by injection of STZ ip after rats had received uninephrectomy. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), and 24-h proteinuria (24hUpro) were observed in the rats at week 4, 8, and 12, respectively. Creatinine clearance (Ccr), the kidney weight (KW), profile of kidney hypertrophy (KW/BW), renal tissue protein contents (RTP), glomerular area (AG), glomerular volume (VG), and width of glomerular basement membrane (GBM) were determined after the rats were sacrificed at week 12. Renal expression of connective tissue growth factor (CTGF) and transforming growth factor-beta1 (TGF-beta1) were determined by immunohistochemistry. RESULTS: There was no significant difference in BG between group DN and DNI (P >0.05). Irb prevented the increasing of Ualb excretion, 24 hUpro, and Ccr in diabetic rats ( P < 0.01). Furthermore, Irb markedly inhibited the increasing of KW, KW/BW, RTP, AG, and VG shown in diabetic rats (P <0.05, P <0.01, respectively). Irb prevented the thickening of GBM and immunostaining of CTGF (P <0.01). The extent of CTGF expression was positively correlated with the glomerular immunostaining for TGF-beta1 and size of VG (P <0.01). CONCLUSION: Irb exerts an early renal protective role to diabetic nephropathy, possibly through inhibition of renal hypertrophy and expression of CTGF.
AIM: To investigate the mechanisms of angiotensin II receptor antagonist irbesartan (Irb) in prevention of renal lesion in streptozotocin (STZ)-induced diabeticrats. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: normal control (group N), diabetic nephropathy (group DN), and diabetic nephropathy treated with Irb (group DNI). Diabetes was induced by injection of STZ ip after rats had received uninephrectomy. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), and 24-h proteinuria (24hUpro) were observed in the rats at week 4, 8, and 12, respectively. Creatinine clearance (Ccr), the kidney weight (KW), profile of kidney hypertrophy (KW/BW), renal tissue protein contents (RTP), glomerular area (AG), glomerular volume (VG), and width of glomerular basement membrane (GBM) were determined after the rats were sacrificed at week 12. Renal expression of connective tissue growth factor (CTGF) and transforming growth factor-beta1 (TGF-beta1) were determined by immunohistochemistry. RESULTS: There was no significant difference in BG between group DN and DNI (P >0.05). Irb prevented the increasing of Ualb excretion, 24 hUpro, and Ccr in diabeticrats ( P < 0.01). Furthermore, Irb markedly inhibited the increasing of KW, KW/BW, RTP, AG, and VG shown in diabeticrats (P <0.05, P <0.01, respectively). Irb prevented the thickening of GBM and immunostaining of CTGF (P <0.01). The extent of CTGF expression was positively correlated with the glomerular immunostaining for TGF-beta1 and size of VG (P <0.01). CONCLUSION: Irb exerts an early renal protective role to diabetic nephropathy, possibly through inhibition of renal hypertrophy and expression of CTGF.
Authors: Hesham M El-Shewy; Mimi Sohn; Parker Wilson; Mi Hye Lee; Samar M Hammad; Louis M Luttrell; Ayad A Jaffa Journal: Mol Endocrinol Date: 2012-03-15