Effects Of Telmisartan And Pyridoxamine On The Level Of AGEs, RAGE And The Early Damage Of Kidney In Spontaneously Hypertensive Rats

ObjectiveThe purpose of this study was to explore the influence of AGEs and RAGE on the development of early kidney structural and functional damage in hypertension and to investigate the effect of telmisartan and pyridoxamine administrated separately and jointly on early renal damage in spontaneously hypertensive rats.MethodsForty-eight 22-week-old male SHRs were randomized into 4 groups. Rats in hypertensive control group (HC group) were received 2ml H20 everyday. Rats in telmisartan group (T group)were received telmisartan 6mg/kg in 2ml H20 everyday. Rats in pyridoxamine group (P group) were received pyridoxamine 200mg/kg in 2ml H20 everyday. Rats in TP group were received telmisartan 6mg/kg and pyridoxamine 200mg/kg in 2ml H20 everyday. Thirteen WKY rats of the same gender and age were received 2ml H20 each day as a normal control group(NC group). Drug treatment lasted for 16 weeks. The serum AGEs,SOD,MDA and 24h-urine micro-albumin were measured after experiment. The structural changes of renal cortex tissues were observed under the light and electron mircoscope. The expression of NF-κBp65 and ERK1/2 in renal cortex tissues were detected with immunohistochemical method. The RAGE mRNA in renal cortex tissues were measured by real-time fluorescence quantitative PCR. Western blot was used to examine the expression of TGF-β,RAGE. All statistical analyses were performed with SPSS version 16.0 software and we set the significance level at 0.05.Results1. The SBP and 24h-urine micro-albumin in HC group were significantly higher than that in NC group(P<0.01). The SBP and 24h- urine micro-albumin in T group and TP group were lower than that in HC group(P<0.01).But P group only had lower 24h-urine micro-albumin(P<0.01) without significance change on SBP(P>0.05).2. There was a positive correlation between 24h-urine micro-albumin and the level of serum AGEs(R=0.9758).3.The serum AGEs and RAGE mRNA in renal cortex tissues in HC group were significantly higher than that in NC group(P<0.01). Telmisartan and pyridoxamine administrated separately and jointly decreased levels of them(P<0.01). Both P and TP group maintained more significance than T group(P<0.05).4. The serum SOD activity in HC group was significantly lower than that in NC group(P<0.05). T group,P group and TP group had higher SOD activity than HC group(P<0.05). The MDA level in serum and renal cortex tissues in HC group were higher(P<0.05). T group,P group and TP group had same lower MDA level than that in HC group(P<0.05).5.There were some pathological changes in renal glomerulus, kidney tubules and interstitium in HC group. The morphological changes were improved in T group,P group and TP group.6.HC group had a highest level of NF-κBp65 measured by Semi-quantitative immunohistochemistry(P<0.01),while T group and P group had a lower one(P<0.01).TP group had a lowest one(P<0.01).7.HC group significantly increased the level of ERK1/2 measured by Semi-quantitative immunohistochemistry(P<0.01). T group was lower than HC group(P<0.01),higher than P group(P<0.01).TP group had lowest one(P<0.01).8.The expression of TGF-βin HC group was significantly higer than that in NC group(P<0.01),while T group,P group and TP group had the same lower expression of TGF-β(P<0.01).ConclusionThe single administration of telmisartan and pyridoxamine can reduce the 24h- urine micro-albumin and improve the morphological changes of renal glomerulus and interstitium in spontaneously hypertensive rats. These effects are associated with the improvement of oxidative stress,the decreasing of AGEs-RAGE and the down-regulated activation and expression of ERK1/2, NF-κBp65 and TGF-β.Telmisartan can decline the level of SBP, while pyridoxamine had no such effect.Compared with the single administration of telmisartan and pyridoxamine, the simultaneous administration showed improved effects on declining the expression of ERK1/2 and NF-κBp65 in renal cortex tissues.But there was no sigifincance between those two methods in the observation of 24h-urine micro-albumin and the expression of .TGF-βin renal cortex tissues.