Effect Of Rosiglitazone On Concentration Of Resistin And Renal Protection In Type 2 Diabetic Rats

Objective:To observe the concentration of resistin and CRP, and the expression of PAI-1 in streptozotocin-induced diabetic rats,to study the protective effect of rosiglitazone on kidneys of type 2 diabetic rats,and to explore the underlying mechanisms.Methods:Thiety-two male health SD rats were chosen as study objects. They were randomly divided into three groups:(l)Control group (CON Group,n=8),fed with a standard chow. And injected with citrate butter (40mg/kg) at forth week;then after six weeks,received equal volume distilled water by daily gavage;(2)Diabetes mellirus group( DM group n=10), The others(24 rats) induced by intraperitoneal injection(ip)of STZ (40mg/kg) after four weeks with high fat chow feeding. There were 20 diabetic rats whose fasting blood glucose was above 10mmol/l ad 3 vic after six weeks. Then randomly chose ten rats as DM group, received equal volume distilled water by daily gavage;(3)RSG group(n=10),diabetic rats treated with 4mg/kg rosiglitazone by dialy gavage. They were observed for fourteen weeks. At the beginning of the experiment,body weight (WT),fasting blood glucose (FBG),fasting insulin(FINS),total cholesterol (TC), triglyceride (TG) and the quantity of 24hr urinary microalbu- minuria(24hr-MAU) were measured, the same at the sixth week and at the fourteenth week,and calculate HOMA-IR and ISI. The rats were killed at the end of fourteenth week,examine the concentration of serum resistin,CRP and the expression of PAI-1 in renal tissues by immunohistological analysis,observe the change of pathology of renal in different groups .Results:1. At 6 weeks,compared with Con group and the basic, the levels of FBG,FINS and TC were markedly increased (P<0.01); HOMA-IR and 24hr-MAU were markly increased and ISI was lowed compared with Con group(P<0.05).In RSG group,compared with DM group,FINS,HOMA-IR and 24hr-MAU were decreased(P<0.05),ISI increased(P<0.01),FBG decreased,but didn't achieve significant statistic differences atl4 weeks;2. At 14 weeks,compared with Con group(7.53±1.99),the concentration of serum resistin(ng/ml) was significant increased in DM group (50.47±17.6)and in RSG group(32.37±22.13)(P<0.01),but in RSG group,it was decreased compared with DM group (P<0.05);3 . At 14 weeks,the concentration of CRP(mmol/l) in DM group(4.23±1.35) was significant increased compared with Con group (1.86±0.54)(P<0.01); whereas in RSG group(2.66±1.17) it was decreased compared with DM group(P<0.01);4. The basic concentration of 24hr-MAU in three groups was no significant statistic differences; After 6 weeks, the concentration of 24hr-MAU was significant increased in diabetic rats (P<0.01respectively), and increased following process of disease in DM group; and at 14 weeks ,it was no significant statistic differences in RSG group compared with at 6 weeks, ,but decreased compared with DM group(P<0.01);5. light microscopy shows: compared with Con group,inflammatory cell infiltrate, glomerular sclerosis, nephric tubule necrosis fibrosis, thickening of glomerular basement membrance in DM group. These changes in RSG group significantly ameliorated compared to DM group;6. The expression of PAI-1 in renal tissues of diabetic rats was higher than that of Con group (p<0.01),while PAI-1 expression of RSG group was lower than that of DM group rats(p<0.01);7. There was positive correlation between resistin with CRP, HOMA-IR,FBG and FINS (r=0.493,0.720,0.608,0.680;P<0.01 respectively), negative correlation between resistin with HDL,ISI and gray scale figure of PAI-l(r=-0.593,-0.744, -0.656;P<0.01 respectively); There was negative correlation between CRP with gray scale figure of PAI-1 (r=-0.589, P<0.05); There was positive correlation between 24hr- MAU with resistin and CRP (r=0.518,0.661;P<0.05 respectively),negative correlation with gray scale figure of PAI-l(r=-707;P<0.01);8. Multiple linear stepwise regression analysis showed that there was positive correlation between resistin with FBG (r=1.379,P<0.01); negative correlation with HDL and gray scale figure of PAI-1 (r=-60.481,-0.225;P<0.05 respectively). Conclusion:1. The concentration of resistin was increased in type 2 diabetic rats;2. Rosiglitazone improve insulin resistance;3. Rosiglitazone have protective effect on kidneys of type 2 diabetic rats by improving insulin resistance;attenuating inflammatory reaction and suppressing the expression of PAI-1..