Effects Of Rosiglitazone On Receptor For Advanced Glycation End Products (RAGE) In Renal Tissue Of Diabetic Rats

OBJECTIVE AND BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication in long-standing diabetic patients who eventually undergo renal dialysis or transplantation, and is one of the most common causes of end-stage renal disease in the world. It causes disability, shortens life expectancy, and reduces quality of life. The pathogenesis of diabetic nephropathy is still unclear. Studies have revealed that advanced glycation and oxidative stress have been implicated in the development of diabetic nephropathy. Advanced glycation end products (AGEs) inducing renal hypertrophy and glomerulosclerosis by accumulating in renal cortex, mesangial region, glomerular basement membrane and lesion vessels. The interaction of AGEs and its receptor (RAGE) activates the second signal system, produces lots of cytokines, does impairment to renal glomerulus and tubule irreversibly. Therefore, limiting RAGE expression might be an intriguing concept to modulate DN in diabetic patients. Rosiglitazone, one of thiazolidinediones(TZDs) compound, isused as antidiabetic agent that attenuates insulin resistance and lipometabolism. Recent studies have revealed that TZDs can block AGE formation, inhibit oxygenation, alleviate proteinuria, inhibit mesangial cell hyperplasia and extracellular matrix synthesis by activating peroxisome proliferator-activated receptor -gamma (PPARγ), thus postponing the development of diabetic nephropathy. The aim of the present study was to determine whether rosiglitazone affects expression of RAGE in nephridial tissue of streptozotocin-induced diabetic rats. RESERCH DESIGN AND METHODS : We induced Diabetic rats by an intraperitoneal injection of streptozotocin (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 (DL group, intragastric administration rosiglitazone 5mg/kg.d) and Diabetes group (D group) and normal control group (C group). The body weight and blood glucose were measured every two weeks. 8 weeks later, all rats were killed and the expression of RAGE was semiquantified in nephridial tissue by reverse transcription-polymerase chain reaction (RT-PCR), and renal morphology was evaluated by immunohistochemistry respectively.RESULTS:1. The RAGE expression was increased in nephridial tissue of diabetic rats. RAGE/β-actin ratio of diabetic group was significantly higher than that of the control (P<0.01), and the percentage and density of cells positive for RAGE in the renal cortex was greater in the diabetic groups than in the control ones (P<0.01).2. After treatment with rosiglitazone, RAGE expression decreased significantly.CONCLUSIONS:1. The high expression of RAGE may participate in the renal damage of diabetic rats.2. In C group, RAGE almost expressed in glomeruli only, when in diabetic rats, glomeruli and tubule were both involved.3. Rosiglitazone have no effect on the level of serum glucose, but significantly down-regulate RAGE expression in renal. It may have some renal protective effect on diabetic nephropathy, partly through inhibition of excessive expression of RAGE in nephridial tissue.