Effects Of Pioglitazone On Receptor Of The Advanced Glycation End Products In Renal Cortex Of Streptozotocin-induced Diabetic Rats

OBJECTIVE AND BACKGROUNDDiabetic nephropathy (DN) is one of the diabetic microvascular complications, which is responsible for many of the disabilities and short life expectancy associated with diabetes mellitus. As is diabetes itself, diabetic nephropathy is a multifactor disease. Studies have revealed that the advanced glycation end products (AGEs) participate in the pathogenesis of nephropathy through several mechanisms, including their binding to the specific receptors (RAGE). Therefore, limiting RAGE expression might be an intriguing concept to modulate DN in diabetic patients. Pioglitazone, a thiazolidinedione (TZDs) compound, is a newly developed antidiabetic agent that attenuates insulin resistance. Recent studies have revealed that TZDs can reduce RAGE expression in human endothelial cells, thus limiting the cells' susceptibility toward proinflammatory AGE effects. The aim of the present study was to determine whether pioglitazone affects RAGE mRNA in renal cortex of streptozotocin-induced diabetic rats. RESERCH DESIGN AND METHODSWe induced Diabetic rats by an intraperitoneal injection of STZ in Sprague-Dawley (SD) rats. The criterion of diagnosis of diabetes was the consecutive blood glucose level≥16.7 mmol/L. 30 male SD rats were randomly divided into 3 groups: diabetes adding pioglitazone group(n=9, intragastricadministration pioglitazone 20mg/kg.d), diabetes group(n=9) and normal control group(n=10). The body weight and blood glucose were measured every two weeks. 8 weeks later, all rats were killed and the expression of RAGE mRNA was quantified in renal cortex by reverse transcription-polymerase chain reaction (RT-PCR) respectively. RESULTS1. The RAGE mRNA expression was increased in renal cortex of diabetic rats. RAGE/p-actin ratio of diabetic group was significantly higher than that of the control (PO.01).2. After treatment with pioglitazon, RAGE mRNA expression decreased significantly and RAGE/p-actin ratio was obviously lower than that of the control. CONCLUSIONS1. The high expression of RAGE mRNA may participate in the renal damage of diabetic rats.2. Pioglitazone can protect the renal tissue by reducing receptor of the adnanced glycation end products (RAGE).