LOSARTAN PREVENTS CHRONIC PROGRESSIVE KIDNEY LESION IN ADRIAMYCIN-INDUCED NEPHROPATHY BY DECREASING THE EXPRESSION OF TGF-beta 1

Li Zhi-Hui, Yi Zhu-Wen

Laboratory of Pediatric Nephrology, The Second Hospital of Xiang Ya School of Medicine, Central South University, Changsha, China

 

Objective: To investigate the role of RAS in chronic renal injury and the relation between RAS and TGF-beta1 on renal with nephrotic syndrome.

Methods: 85 male SD rats were randomly divided into three groups: group I: adriamycin-induced nephropathy, group II: losartan-treated nephropathy, group III: control rats. Four animals every group were sacrificed every 4 weeks. Body wt and 24h urinary protein were measured. Serum chlesterol(CHO), albumine, urea nitrogen(BUN) and creatinine(Scr) were examined. Renal TGF-beta1 and angiotensinogen mRNA expression were assessed. Protein expression of TGF-beta1 in renal were assessed by immunohistochemical method. A semiquantitative score was used to evaluate the degree of glomerular sclerosis and tubulointerstitium lesion.

Results: In contrast to control, 24h urinary protein, the kidney wt, serum CHO, BUN and Scr were increased both in the group I and group II (P<0.01), it was higher in the group I than in the group II (P<0.01). Glomerular sclerosis and tubulointerstitium lesion in the group I were more seriously than in the group II (P<0.01). Expression of angiotensinogen mRNA in renal was gradually increased in accordance to the order from control, losartan-treated nephropathy and adriamycin-induced nephropathy (P<0.01). After 11 weeks, TGF-beta1mRNA expression in renal was gradually increased both in the groupand group II versus in the group III (P<0.01), and it was the highest in the group I (P<0.01). The percentage of TGF-beta1 positive staining cells in renal both in the group I and group I significantly increased versus  in the group III (P<0.01), it was higher in the groupthan in the group II (P<0.01).

Conclusions: The persistently increased angiotensinogen and TGF-beta1 mRNA expression in renal play an important role in the kidney irreversible injury of adriamycin nephropathy rat. The increase of RAS activity in situ could induce TGF-beta1 production in renal. 

 

 
2345