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 groupⅠand 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 groupⅠthan 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.