Study On Rosiglitazone In Prevention Of Renal Lesion In Streptozotocin-induced Diabetic Rats

ObjectiveThe aim of this study was to investigate the serum level of solubleintercellular adhesion molecule-1 (sICAM-1) and the expression ofplasminogen activator inhibitor-1(PAI-1) in streprozotocin-induceddiabetic rats,to study the protective effect of rosiglitazone on kidneys ofstreprozotocin-induced diabetic rats and to explore the underlyingmechanisms.MethodsForty male health SD rats were randomly divided into fourgroups:(1)Control group (Con Group,n=8),fed with a standard chow forfourteen weeks.(2)High fat chow group(HF Group,n=8),fed with extrahigh fat chow containing 10％lard,10％yolk powder and 20％sugar.(3)Diabetes mellitus group(DM Group,n=14), (4) Rosiglitazonegroup (RSG Group,n=10).The diabetic rats were induced byintraperitoneal injection(ip)of STZ (40mg/kg) after four weeks of high fatchow feeding.The rats in Con group and HE group were injected withequal volume of sham citrate buffer.72 hours later, the rats whose fastingblood glucose was above 10mmol/1 ad 3 vic were identified as diabeticrats,whereas those whose fasting blood glucose were less than 10mmol/1were excluded.There were 20 diabetic rats. The RSG group were treated with 4mg/kg rosiglitazone by dialy gavage for 8 weeks.The other theregroup received equal volume of distilled water.During the period of theexperiment, free food and water without insulin were given to theserats.Body weight(WT),fasting blood glucose (FBG),fastinginsulin(FINS),total cholesterol(TC), triglyceride (TG), serum ureanitrogen(SUN) serum creatinine(sCr),the volume of twenty-four-hoururine and the quantity of twenty-four-hour urinarymicroalbuminuria(24hr-MAU) were measured at the beginning,the sixthweek and the end of fourteenth week of the experiment. Serum sICAM-1was determined by enzyme-linked immunosorbent assay(ELISA).Thechange of renal pathology was observed by light microscope,and theexpression of PAI-1 in renal tissues were examined byimmunohistological analysis.Results1.Variation of blood biochemistry(1)At the sixth and the fourteenth week, diabetic rats were thinnerthan HF group(p＜0.05). Compared with the rats in Con group, theserum concentrations of TG, TC and FINS and HOMA-IR of diabeticrats were significantly increased (p＜0.05).These rats were inducedinsulin resistance. But there was no statistical difference between theDM group and RSG group (p＞0.05),in the rats of RSG group,therewas no statistical difference between the sixth week and the fourteenth week,which indicated that rosiglitazone did not influence lipidmetabolism on these diabetic rats.(2)At the sixth and the fourteenth week, fasting blood glucose ofdiabetic rats was highest than the other two groups(p＜0.05).These ratshad the features of diabetic mellitus.The achievement ratio of rat modelattain 83.3％. But there was no statistical difference between the DMgroup and RSG group (p＞0.05),in the rats of RSG group,there was nostatistical difference between the sixth week and the fourteenthweek,which indicated that rosiglitazone did not influence glucosemetabolism on these diabetic rats.(3)At the sixth and the fourteenth week, the volume oftwenty-four-hour urine and the quantity of twenty-four-hour urinarymicroalbuminuria of diabetic rats were higher than that in Con groupand HF group(p＜0.05). But there was no statistical difference of thevolume of twenty-four-hour urine between the DM group and RSGgroup (p＞0.05), between the sixth week and the fourteenth week of therats in RSG group,The quantity of twenty-four-hour urinarymicroalbuminuria of the rats in RSG group was much lower than that inDM group(p＜0.05). There was no statistical difference of serum ureanitrogen and serum creatinine between four groups and different time(p＞0.05).2.The level of sICAM-1 was significantly increased in DM group compared with the Con group and HF group(p＜0.05).Administrationwith rosiglitazone significantly decreased the serum sICAM-1level(p＜0.05).3.The pathology changes in renal of the diabetic rats includedglomerular sclerosis and renal tubular necrosis.These changes in RSGgroup were significantly ameliorated as compared to DM group(p＜0.05).4.The expression of PAI-1 in renal tissues of diabetic rats was higherthan that of Con group and HF group(p＜0.05),while PAI-1 expression ofRSG group was lower than that of DM group rats(p＜0.05).5.The quantity of twenty-four-hour urinary microalbuminuria waspositively correlated with serum sICAM-1 (r=0.415,p＜0.05)andnegatively correlated with the expression of PAI-1(r=-0.675, p＜0.05)ConclusionRosiglitazone could significantly reduce the quantity of 24hr urinarymicroalbuminuria of STZ-induced experimental diabetic rats withoutdecreasing the level of fasting blood glucose and plasma lipid.Rosiglitazone exhibit direct renal protective effect possibly throughdownregulating serum sICAM-1 level and suppressing the expression ofPAI-1 in renal.