Effects of Losartan on the Expression of Phosphorylated P38 Mitogen-activated Protein Kinase in Renal Tubulointerstitium in Experimental Diabetic Rats

【Objective】To investigate whether p38 MAPK is associated with the development of tubulointerstitial lesions and the effects of Losartan on the expression of the phosphorylated p38 MAPK in renal tubulointerstitium in experimental diabetic rats.【Methods】Male Wistar rats were randomly divided into two groups: control and diabetic group.Diabetes was induced by intraperitoneal injection of STZ.Diabetic group was divided into diabetic and Losartan treatment group.Eight weeks later,samples were collected to determine urinary protein excreted in 24 hours and serum creatinine.A portion of renal tissue was analyzed with hematoxylin eosin stain and Masson stain.The extent of tubulointerstitial injury was evaluated and graded.levels of phosphorylated p38 and transforming growth factor-beta1(TGFβ1) were assessed by Immunohistochemistry in rats.Computer image-pattern analysis system was used to analyze the expression of P-P38 MAPK and TGF-β1 in renal tubulointerstitium.【Results】①The amount of urinary protein excreted in 24 hours and the tubulointerstitial lesions and the accumulation of extracellular matrix protein were significantly greater in diabetic rats than in control rats(P0.01)②Expression of P-p38 MAPK in diabetic tubulointerstitium in diabetic rats was higher than in the controls,the same as the expression of TGF-beta1(P0.01).③After Losartan treatment,urinary protein excreted in 24 hours and the tubulointerstitium lesions and the accumulation of extracellular matrix protein was ameliorated,and the expressions of P-P38 MAPK as well as TGF-beta1 were markedly decreased compared with diabetic group(P0.01).【Conclusion】These results suggest p38MAPK phosphorylation and the up-regulation of TGF beta1 contribute to the development of tubulointerstitial lesions in diabetic nephropathy;inhibition of tubulointerstitial p38 MAPK activation and the expression of TGF beta1 may be responsed for the renal protective effects of Losartan in experimental diabetic nephropathy rats.