Effects Of Rosiglitazone On Receptor For Advanced Glycation End Products (RAGE) In Retina Of Streptozotocin-induced Diabetic Rats

Objective and BackgroundDiabetic retinopathy(DR) is one of the major diabetic complications,which is responsible for many of the disabilities and blindness associated with diabetes mellitus. As is diabetes itself,diabetic retinopathy is amultifactor disease.Studies have revealed that the advanced glycation end products(AGEs) participate in the pathogenesis of diabetic retinopathy through several mechanisms,including their binding the specific receptors(RAGE).Therefore,limiting RAGE expression might be an intriguing concept to modulate diabetic retinopathy in diabetic patients.Rosiglitazone,a thiazolidinedione (TZDs) compound,is a newly developed antidiabetic agent which attenuates insulin resistance.Recent studies have revealed that TZDs can reduce RAGE expression in human endothelial cells,thus limiting the cells' susceptibility toward proinflammatory AGEs effects.The aim of the present study is to determine whether rosiglitazone affects RAGE mRNA in retina of streptozotocin(STZ)-induced diabetic rats. Research Design and MethodsWe induced Diabetic rats by an intraperitoneal injection of STZ in SD rats.The criterion of diagnosis of diabetes was the consecutive blood glucose level≥16.7 mmol/L. 27 male SD rats were randomly divided into 3 groups,Diabetes adding rosiglitazone group(n=9,intragastric administration rosiglitazone 5mg/kg.d),Diabetes adding NS group(n=9) and normal control group(n=9).The body weight and blood glucose were measured every two weeks.8 weeks later,all rats were killed and the eyeballs were removed.The expression of RAGE mRNA was quantified in retina by reverse transcription-polymerase chain reaction(RT-PCR) respectively.Results1.The RAGE mRNA expression was increased in retina of diabetic rats. RAGE/β-actin ratio of diabetic group was significantly higher than that of the control (P＜0.01).2.After treatment with rosiglitazone,RAGE mRNA expression decreased significantly and RAGE/β-actin ratio was obviously lower than that of the control.Conclusions1.The high expression of RAGE mRNA may participate in the retina damage of diabetic rats.2.Although rosiglitazone has no effect on the level of serum glucose,it can significantly down-regulate RAGE expression in retina.It may protect the retina from the impairment of advanced glycation end products.