Renoprotective effect of rosiglitazone through the suppression of renal intercellular adhesion molecule-1 expression in streptozotocin-induced diabetic rats

Abstract

To observe the effect of rosiglitazone on 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. Twenty-four Wistar Rats were divided into 3 groups: non-diabetic control rats (group A, no.=8), streptozotocin-induced diabetic rats (group B, no.=8), and diabetic rats treated with rosiglitazone (group C, no.=8). Rats in group C were treated with rosiglitazone (5 mg x kg(-1) x d(-1)) 1 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 (HbA1c) and SICAM-1 as well as urinary albumin excretion rate (UAER), urinary retinol binding-protein (URBP) excretion rate, and urinary ICAM-1 (UICAM- 1) excretion rate were tested at the 8th week, and the renal tissues of all rats were obtained for evaluating kidney/body weight ratio, observing pathologic change via electron microscope, and for examining the expression of ICAM-1 mRNA by reverse transcriptase-PCR. At the 8th week, the blood glucose, HbA1c levels, UAER, URBP excretion rate, kidney/body weight ratio and serum, urinary ICAM-1 levels all increased significantly in group B and group C in comparison with group A; however, the above-mentioned parameters in group C (except the blood glucose and HbA1c levels) were much lower than those in group B. In addition, both SICAM-1 and UICAM-1 were highly correlated with the UAER, URBP level, and kidney/body weight ratio in all rats; renal pathological lesions observed by electron microscope in group C were much lighter than those of group B; compared with group A, the expression of ICAM-1 mRNA was markedly up-regulated in group B and group C, and rosiglitazone was able to decrease the expression of ICAM-1 mRNA in the renal tissue. Rosiglitazone could 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 ICAM-1 productions in both serum and urine.