| Objective To observe the effect of rosiglitazone on the serum intercellular adhesion molecule-1 (SICAM-1) level, urinary excretion of ICAM-1 and renal expression of ICAM-1, and investigate its possible renoprotective mechanisms in diabetic rats.Method 24 Wistar Rats were divided into three groups: non-diabetic control rats (group A, n=8), streptozotocin-induced diabetic rats (group B, n=8) and diabetic rats treated with rosiglitazone (group C, n=8). Each rat in groups B and C received an intraperitoneal injection of Streptozotocin (STZ) to establish type 1 diabetic models. Rats in group C were treated with rosiglitazone (5mg.kg-1.day-1). One week after the establishment of diabetic model, group A and B were treated with corresponding sodium chloride. Peripheral blood glucose was tested weekly. Glycosylated hemoglobin A1c(HbA1c) and SICAM-1 level as well as urinary albumin excretion rate (UAER), urinary retinol binding-protein (URBP) excretion rate and urinary intercellular adhesion molecule-1(UICAM-1) excretion rate were tested at the 8th week, and the renal tissues of all rats were obtained partly for evaluating kidney/body weight ratio, observing pathologic changes via light microscope and electron microscope, partly for examining the expression of ICAM-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR).Results1. The blood glucose levels at the 2nd, 4th, 8th weeks and HbA1c level at the 8th week in group B and group C were significantly higher compared with those of group A (P<0.01), and there's no statistical differences between groups B and C(P>0.05), including both of the blood glucose and HbA1c levels.2. UAER, URBP excretion rate, UICAM-1 excretion rate, SICAM-1 level and kidney/body weight ratio at the 8th week in groups B and C increased significantly compared with those in group A (P<0.01). Treatment with rosiglitazone significantly reduced the SICAM-1 level and urinary excretion rate of ICAM-1 as well as kidney/body weight ratio and urinary excretion rates of ALB, RBP (P<0.01). In addition, SICAM-1 level showed positive correlations with UAER (r=0.882, P<0.01), URBP excretion rate (r=0.884, P<0.01) and kidney/body weight ratio (r=0.920, P<0.01) and UICAM-1 excretion rate also showed positive correlations with UAER (r=0.907, P<0.01), URBP excretion rate (r=0.900, P<0.01) and kidney/body weight ratio (r=0.950, P<0.01).3. The light microscopes results showed that there's no pathological lesion found in group A. Pathological changes were much more obvious in group B. It was clear that the glomerular capillary loops were tumbling, lumens blocked, mesangial region widened, basal lamina thickened, mesenterium base increased, the volume of glomerulus became larger and the cell population increased significantly. It also can be observed that the renal tubule was vacuolization and the renal interstitium was infiltrated by lots of lymphocytes and emononuclear macrophages. Pathological changes in group C were lighter, it can be observed that glomerular capillary lumen was constrictive slightly and few lymphocyte infiltrated.4. The electron microscopes results showed that the structure and width of glomerular basement membrane (GBM), epithelial foot processes (FP) as well as the mesangial region were normal in group A at the 8th week. In group B, however, the FP fusion rate was approximately 80 percent and the thickening of GBM were observed. In addition, it was noted that some FP were destroyed, even vanished, the ultrastructure of GBM became ambiguous, the mesangial cells swelled and the extracellular matrix accumulated which caused mesangial region to expand intensively. After the treatment of rosiglitazone, the thickness of GBM in group C decreased markedly compared with that in group B. It was clear that the ultrastructure of GBM was relatively regular, only 20 percent of the epithelial foot processes fused and the expansion of the mesangial region was unconspicuous.5. Compared with group A, the expression of ICAM-1 mRNA was markedly up-regulated in group B and group C (P<0.01), and rosiglitazone could decrease the expression of ICAM-1 mRNA in the renal tissue (P<0.01).Conclusion The overexpression of ICAM-1 protein and mRNA in renal tissue of diabetic rats may be one of the mechanisms of diabetic nephropathy. Rosiglitazone definitely protect against the renal injury of diabetic rats, which may be partly associated with decreasing the expression of ICAM-1 in the renal tissue, reducing SICAM-1 level and the urinary excretion of ICAM-1, independently of its hypoglycemic effect. |
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