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Objective:The main aim of this study was to investigate the changes about excretion of urine protein,renal function and the expressions of nephrin and cyclooxygenase-2(COX-2)in rats with diabetic nephropathy(DN),and the relationship among these changes, study the effects and mechanisms of rosiglitazone and all-trans retinoic acid on diabetic nephropathy.Methods:(1)To establish streptozotocin-induced diabetic rats model by intraperitoneal injection of streptozotocin(55mg/kg).The model rats were divided randomly into 3 groups:rosiglitazone-treated group(R group),all-trans retinoic acid-treated group(A group),and model control group(D group),nomal rats group(N group)served as control.(2)Eight weeks later,blood glucose,serum lipid profile, excretion of urine protein and renal function were detected,and the histopathological changes of kidney were also detected with optic microscope.The expressions of nephrin and COX-2 protein were detected by immunohistochemistry and the expressions of nephrin and COX-2 mRNA were detected by Real-time PCR.Results:(1)Compared with normal rats,blood glucose,excretion of urine protein,blood urea nitrogen(BUN)and serum creatinine(Scr)were significantly increased,and creatinine clearance rate(Ccr)was decreased in D gruop.In addition,renal histopathological changes in D gruop were similar to those of diabetic nephropathy.(2)The expressions of nephrin protein and mRNA in the kidney of D group were both lower than N group(all P<0.05),whereas the expressions of COX-2 protein and mRNA in the kidney of D group were higher than N group(all P<0.05).(3)8 weeks later,the excretion of urine protein,BUN and Scr in R,A groups were lower than D group(all P<0.05),Ccr was higher than D gruop(all P<0.05);The excretion of urine protein,BUN,Scr and Ccr did not differ significantly between R and A group(all P>0.05).The expressions of nephrin protein and mRNA in R,A groups were higher than D group(all P<0.05);while the expressions of COX-2 protein and mRNA were lower than D group(all P<0.05).The expressions of nephrin and COX-2 did not differ significantly between R and A group(all P>0.05).(4)Respectively compared with D group,blood glucose, triglyceride,total cholesterol,high density lipoprotein cholesterol and low density lipoprotein cholesterol in R,A groups did not differ significantly (all P>0.05).(5)In D,R,A groups,the levels of nephrin protein and mRNA were significantly negative correlated with 24h urine protein excretion(r=-0.647,P<0.05;r=-0.800,P<0.05)and the levels of COX-2 protein and mRNA were positive correlated with 24h urine protein excretion(r=0.624,P＜0.05;r=0.569,P＜0.05).Conclusion:Rosiglitazone and all-trans retinoic acid all may decrease proteinuria,improve renal function,alleviate renal histopathological damage and retrieve the changes of nephrin and COX-2 expressions to alleviate renal filtration barrier function and hemodynamic indexes in DN rats,but they do not significantly change blood glucose and serum lipid profile in all treated groups.Rosiglitazone and all-trans retinoic acid may up-regulate nephrin expression and down-regulate COX-2 expression to produce direct nephroprotective effect independent of glucose and lipid metabolism.The favorable effect of rosiglitazone is similar to all-trans retinoic acid.
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