The Study Of Renoprotective Effects Of Angiotensin Ⅱ Receptor Antagonist On Diabetic Rat And Its Mechanism

The aim of the study was to investigate the renoprotective effects of losartan on the kidney of diabetic rat and its renoprotective mechanism.The rats were randomly divided into following groups:normal control rats(group C.)streptozotocin diabetic rats (group DM) and diabetic rats treated with losartanl group DL).After eight weeks.the expression of transforming growth factor-β₁ (TGF-β₁) .type I TGF-β receptor(T β RI). type â…¡ TGF-β receptor (T β Râ…¡)and fibronectin mRNA in renal cortices of all three groups were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). The expression of transforming growth factor- B i(TGF- B f) .T (3 RI. T B RII and fibronectin protein in renal cortices in all three groups were measured hy histoimmunochemistry.The blood glucose .urea and creatinine were also measured by biochemistry while blood insulin and angiotensin II were measured by radioimmunoassay. The rate of urinary albumin excretion were measured by sulfosalicylic acid assay.After eight weeks, mean glomerular volume, kidney weight ' body weight ratio, urinary albumin excretion ratio, urea and creatinine in the serum were significantly higher in diabtic group than that in normal control group. P (0.05 ). The expression of T 6 RI. T B RII and fibronectin mRNA in renal cortices of diabtic group were significantly increased CP 0.05 ) .The expression ofTGF- 3 i ,T 3 RI, T 3 RII and fibronectin protein of renal cortices in diabtic group were also significantly increased (P (0.05 ). The mean glomerular volume, kidney weight/ body weight ratio, urinary albumin excretion ratio, blood urea and creatinine in diabetic rats were markedly decreased by administration of losartan for eight weeks. The expression of T 3 RI, T 3 RII and fibronectin mRNA in renal cortices of diabtic rats treated with losartan were significantly reduced (P (0.05) . The expression of TGF- 3 i .T P RI, T 3 RII and fibronectin protein in renal cortices in diabtic rats treated with losartan were also significantly diminished (P (0.05) .It suggests that losartan could have protective effects on the kidney of diabetic rat .The renoprotective mechanism might be that losartan downregulates the expression of TGF- 3 system which results in inhibition of renal hypertrophy and reduction of the biosynthesis of extracellurlar matrix.