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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Qian
Y
Y
Department of Endocrinology, Anhui Provincial Hospital, Hefei, China.
Li
S
S
Ye
S
S
Chen
Y
Y
Zhai
Z
Z
Chen
K
K
Yang
G
G
D000818:Animals; D019610:Cytoprotection / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D013311:Streptozocin; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin