| AIM: Glomerular hypertrophy and progressive expansion of extracelluar matrix(ECM) have been regarded as the early feature of diabetic nephropathy(DN), which leads to accumulation of mesangium matrix and thickening of glomerular basement membrane(GBM). But the exact mechanism of DN is still to be clarified. Our present study focused on the effect of Irbesartan (Irb), a newly approved product of angiotensin II receptor antagonist (AIIRA), on urinary albumin in excretion, renal hypertrophy and renal expression of matrix metalloproteinase-2 (MMP-2)/tissue inhibitor of metalloproteinase-2 (TIMP-2) in streptozotocin (STZ) induced diabetic rats.METHODS: In the present study, male Sprague-Dawley (SD) rats were randomly divided into three groups: normal control rats (group N,n=8), diabetic rats (group DN,n=9) and diabetic rats treated with Irb (group DNI,n=10). Diabetes was induced by injection of STZ intraperitoneally after rats had received uninephroectomy. Blood glucose, body weight, 24-h urinary albumin excretion (24hUalb),creatinine clearance(Ccr)were observed in the rats at week 8, respectively. The kidney weight (KW), profile of kidney hypertrophy (kidney weight/body weight, KW/BW), the glomerular area (AG) and the glomerular volume (VG) were determined when the rats were sacrificed at week 8. Renal expression of MMP-2 and TIMP-2 was determined by immunohistochemistry. Expression of mRNA for MMP-2 and TIMP-2 was observed by RT-PCR.RESULTS: It was shown that diabetic rats presented with a significantly increase of 24hUalb, Ccr(24hUalb:1.873±0.484 vs 0.048±0.006;Ccr:0.433±0.011 vs 0.121±0.006,P(0.01,respectively) which was markedly prevented by Irb (24hUalb:0.808±0.165 vs 1.873±0.484;Ccr:0.259±0.072 vs 0.433±0.011,P<0.01,respectively). KW, KW/BW and AG, VG were markedly increased in group DN compared with that in group N (KW:3.67±1.04 vs 1.34±0.15;KW/BW×1000:10.11±0.39 vs 2.83±0.78;AG:6.42±0.64 vs 3.58±0.84;VG:60.33±20.22 vs 26.43±6.54,P<0.01 respectively). There was a reduction of all the above parameters in group DNI as compared to that in group DN (KW:2.77±0.24 vs 3.67±1.04 P(0.05;KW/BW×1000:7.61±0.80 vs 10.11±0.39,P(0.01;AG:4.06±0.54 vs 6.42±0.64;VG:36.83±7.98 vs 60.33±20.22,P<0.01 respectively). But KW and KW/BW were still much higher in group DNI than that in group N ( KW:2.77±0.24 vs 1.34±0.15;KW/BW×1000:7.61±0.80 vs 2.83±0.78,P<0.01 respectively). Semi-quantitative assessment of the immunostaining showed that glomerular expression of MMP-2 and TIMP-2 in group DN was significantly increased as compared to that in group N (MMP-2/DN:0.352±0.007 vs N:0.215±0.004; TIMP-2/DN:0.356±0.008 vs N:0.212±0.004,P<0.01 respectively) and much lower in group DNI compared to that in group DN (MMP-2/DNI:0.231±0.006 vs DN:0.352±0.007; TIMP-2/DNI:0.224±0.006 vs DN:0.356±0.008,P<0.01 respectively). Semi-quantitative assessment of expression of mRNA for MMP-2 and TIMP-2 in group DN also was significantly increased as compared to that in group N (MMP-2/DN:0.81±0.01 vs N:0.65±0.03; TIMP-2/DN:0.52±0.04 vs N:0.31±0.04,P<0.01 respectively) which was inhibited by Irb in group DNI(MMP-2/DNI:0.74±0.01 vs DN:0.81±0.01; TIMP-2/DNI:0.35±0.04 vs DN:0.52±0.04,P<0.05 respectively). While the ratio of immunohistochemical and mRNA expression of MMP-2/TIMP-2 was reduced in group DN (immunostaining/DN:0.941±0.036 vs N:1.017±0.019; mRNA/DN:1.57±0.11 vs N:2.16±0.19,P<0.01, P<0.05 respectively)and increased in group DNI (immunostaining/DNI:1.042±0.031 vs DN:0.941±0.036; mRNA/DNI:2.11±0.25 vs DN:1.57±0.11, P<0.01, P<0.05 respectively).CONCLISION: The changes of the expression of MMP-2 and TIMP-2 might play a pathogenetic role in diabetic nephropathy. Irb exerted renal protective role to early diabetic nephropathy, possibly through inhibition of renal hypertrophy, reduction of urinary albumin excretion and glomerular hyperfiltration, and correction the balance of MMP-2/TIMP-2 , subsequently reduced accumulation of ECM.
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