Study On The Effect Of Irbesartan, On The Expression Of GLUT-1 MRNA And TGFβ1 MRNA In The Diabetic Kidneys, And Probe Into Its Mechanism

[Objective]To investigate the effect of Aprovel,a blocker of angiotensin II type-1 receptor,on the expression of glucose transporter-1(GLUT-1) mRNA and transforming growth factor-β1(TGF-β1) mRNA in the diabetic kidney cortex,and probe into its mechanism.[Methods]Forty-eight Wistar rats were divided randomly into normal control group,diabetic control group,Aprovel treated group.Rats in diabetic control group and Aprovel treated group were given STZ(55 mg/kg) by intraperitoneal injection to establish animal model of diabetes.Four rats of each group were sacrificed at the end of the 4th,the 8th,the 12th week and to collect samples,including body weighting, blood sugar,serum creatinine,blood urea nitrogen,cholesterol,triglyceride,24-hour urinary protein excretion.Renal mRNA expression of TGF-βand GLUT-1 were measured with reverse transcriptase-polymerase chain reaction(RT-PCR).HE staining and PAS staining were done to the kidney too.[Results](1)In diabetic control group,the blood sugar,serum creatinine,blood urea nitrogen,cholesterol,triglyceride and 24-hour urinary protein excretion,the renal expressing of GLUT-1 mRNA and TGF-βmRNA increased significantly(p＜0.01).They were observed in HE staining,PAS staining.Kidney pathology:they showed characteristic pathological changes --glomerular hypertrophy, mesangial expansion,vacuolar degeneration of the tubular epithelial cells,all of these suggesting that the rats were in diabetic nephropathy stage.(2) In diabetic rats treated with Aprovel,cholesterol decreased as the time lasted,and showed up difference significantly at the end of the 12th week compared with the 4th week;24-hour urinary protein excretion,serum creatinine and blood urea nitrogen decreased significantly compared with diabetic group at the end of the 4th week,more significantly at the end of the 12th week.Renal expressing of GLUT-1 mRNA and TGF-βmRNA decreased significantly(p＜0.01).Kidney pathological changes improved in HE staining and PAS staining slice.[Conclusion]Aprovel ameliorates renal lesion in diabetic rats,by decreasing serum glucose level and renal mesangial matrix.Aprovel directly suppressed synthesis of TGF-βand down regulating the expression of GLUT-1.The mechanism of Aprovel'effect might be related to the suppression of up-regulated hexosamine biosythesis pathway and to the sup ression of overexp ression of GLUT1.In diabetic rats treated with Aprovel,24-hour urinary protein excretion,serum creatinine and blood urea nitrogen decreased significantly compared with diabetic group.Meanwhile, kidney pathological changes improved and the GLUT1 and TGT- 1 mRNA expression of the kidey were significantly reduced,which suggests Aprovel can effectively prevent or delay the progress of the diabetic nephropathy.