[Influence of irbesartan on renal hypertrophy and thickening of glomerular basement-membrane in streptozotocin-induced diabetic rats].
OBJECTIVE
To investigate the influence of angiotensin II receptor antagonist irbesartan (Irb) on renal hypertrophy and thickening of glomerular basement membrane (GBM) in streptozotocin (STZ) induced diabetic rats.


METHODS
Sprague-Dalwley (SD) rats were randomly divided into three groups: normal control (group N, n = 7), diabetic nephropathy (group DN, n = 6) and diabetic nephropathy treated with Irb (group DNI, n = 7). Diabetes was induced by injection of STZ intraperitoneally after rats had received uninephroectomy. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), 24-hour proteinuria (24hUpro) were observed in the rats at week 4, 8, 12 respectively. Creatinine clearance (Ccr), kidney weight (KW), profile of kidney hypertrophy (KW/BW), renal tissue protein contents (RTP), glomerular area (A(G)), glomerular volume (V(G)), and width of GBM were determined at week 12 when the rats were sacrificed. Renal expression of connective tissue growth factor (CTGF) and transforming growth factor-beta(1) (TGF-beta(1)) were determined by immunohistochemistry.


RESULTS
There is no significant difference of BG between group DN and group DNI (P > 0.05). Irb treatment significantly prevented the increase of Ualb excretion and 24hUpro and the deterioration of Ccr in diabetic rats (P < 0.05, P < 0.01 respectively). 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). More interestingly, we firstly demonstrated that Irb significantly prevented the thickening of GBM [N group: (127.50 +/- 22.14) nm, DN group: (280.38 +/- 52.77) nm, DNI group: (144.07 +/- 24.85) nm] and immunostaining for CTGF (P < 0.05 respectively). In addition, the extent of CTGF expression is positively correlated with the glomerular immunostaining for TGF-beta(1) and size of V(G) (P < 0.01).


CONCLUSIONS
This is the first data to demonstrate that Irb exerts early renal protective role in diabetic nephropathy, possibly through inhibition of renal hypertrophy and renal expression of CTGF.
Liu
Bi-cheng
BC
Renal Division, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Luo
Dong-dong
DD
Sun
Jing
J
Ma
Kun-ling
KL
Ruan
Xiong-zhong
XZ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D006984:Hypertrophy; D000077405:Irbesartan; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan