Effects Of Rosiglitazone On The Renal Injury Of Diabetic Rats And Renal Expression Of Matrix Metalloproteinase-9

Objective To observe the reno-protection and its effect of rosiglitazone on the expression of MMP-9 mRNA in kidney and urinary MMP-9 excretion of diabetic ratsMethod 24 rats were randomly assigned to normal control group(group C); diabetic group(group D) and rosiglitazone treatment group(group R),group R were treated with rosiglitazone(5mg?kg-1?d-1) one week after the establishment of diabetic model,group C and D were treated with corresponding sodium chloride. The urinary excretion rates of albumin(by radioimmunoassy),retinal-binding protein(by ELISA) and matrix metalloproteinase-9 [(MMP-9) by ELISA] were tested at the 2nd week,4th week and 8th week.At the 8th week, all of the experimental rats were killed and renal pathological changes were observed by microscope and electron microscope. The expressions of MMP-9mRNA (by RT-PCR) in renal cortex and the relative kidney (ratio between kidney weight and body weight were tested at the 8th week.Result 1. The blood glucose level of group R were similar with that of group D at the each corresponding time point :2nd, 4th, 8th week ; At the each corresponding time point, the urinary excretion rates of albumin , RBP, MMP-9 all increased in group R and group D compared with those in group C(P<0.01),and rose further as the nephropathy progressed, which in group R were lower than those in group D(p<0.01). The urinary excretion rate of MMP-9 level was highly correlation with the urinary excretion rates of Alb, RBP and relative kidney weight(r=0.832 , P<0.01; r=0.861,P<0.01;r=0.903, P<0.01,respectively).2. In comparison with group C, the expression of MMP-9 mRNA in renal cortex was markedly up-regulated in group D, however, rosiglitazone could decrease the expression of MMP-9 in kidney(P<0.01), The expressions of MMP-9 mRNA in renal cortex was highly correlation with the urinary excretion rate of MMP-9(r=0.824, P<0.01). 3. The light microscopes results showed that pathological changes in group R was light, and glomerular capillary lumen stegnosis lightly, few lymphocyte infiltrating. No pathological lesions were found in group C; pathological changes were much obvious in group D: glomerular capillary lumen tumbling, lumens blocked, mesangial region widened, basal lamina thickening, mesenterium base increased, the volume of glomerulus larged, cell population increased, renal tubule vacuolization, renal interstitium was infiltrated by lots of lymphocyte and mononuclear macrophage.4. The electron microscopes results showed basal lamina uniformity in group R, few foot procss conjugation by about 20%. In group C the basal lamina uniformited, no foot procss conjugation. However in group D the glomerular basement membrane thickening, foot procss overshoot, demolish, confluence, disappeared by about 80% foot procss conjugation. The base material of mesangial region increasing , mesangial region expanding and mesangial cells swelling.Conclusion The overexpression of MMP-9 mRNA in renal cortex of diabetic rats may be one of the mechanisms of diabetic nephropathy. Rosiglitazone can activate PPAR-γand play a protective role on the kidney of diabetic rats,this effect may partly contribute to its down-regulating MMP-9 ,independently of its hypoglycemic effect.