The effects of ACE inhibitor and angiotensin receptor blocker on clusterin and apoptosis in the kidney tissue of streptozotocin-diabetic rats


Tuncdemir M. , Ozturk M.

JOURNAL OF MOLECULAR HISTOLOGY, cilt.39, ss.605-616, 2008 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 39 Konu: 6
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1007/s10735-008-9201-2
  • Dergi Adı: JOURNAL OF MOLECULAR HISTOLOGY
  • Sayfa Sayıları: ss.605-616

Özet

Our first aim was to determine the effects of secreted clusterin (sCLU) and nuclear clusterin (nCLU) in diabetic nephropathy. We also aimed to investigate the post-effects of angiotensin II blockage treatment on clusterin expression and to compare these with apoptosis. Five groups of Wistar albino rats were used: First group consisted of healthy controls; the second group included the untreated STZ-diabetics; 30 days of irbesartan or perindopril treated STZ-diabetics formed the third and the fourth groups, respectively; while the subjects receiving a combined treatment with irbesartan and perindopril for 30 days consisted the fifth group. TUNEL method for apoptosis and immunohistochemical staining for TGF-beta 1, alpha-SMA, clusterin-beta and clusterin-alpha/beta antibodies were performed. Apoptotic cells especially increased in the kidney tubuli of untreated diabetic group and on the contrary, a significant decrease was observed in the group that received a combined drug treatment. While sCLU was increased in the glomeruli and tubuli of the untreated diabetic group, it was decreased in all the treated groups. An increase in the nCLU immunoreactivity was observed in the podocytes, mesangial cells, and the injured tubule cells of the untreated diabetic group. nCLU immunopositive cells were decreased in all treated diabetic groups. In addition to this, the distribution of nCLU was similar to the distribution of apoptotic cells in the diabetic groups. Our results indicate that sCLU expression in diabetic nephropathy was induced due to renal tissue damage, and the nCLU expression increase in renal tubuli was related to apoptosis. Although irbesartan and perindopril prevented further renal injury in diabetes, a combined application of low-dose ACEI and AT1R blockers revealed more efficient measures, by means of renal damage prevention.

 

Our first aim was to determine the effects of
secreted clusterin (sCLU) and nuclear clusterin (nCLU) in
diabetic nephropathy. We also aimed to investigate the
post-effects of angiotensin II blockage treatment on clusterin
expression and to compare these with apoptosis. Five
groups of Wistar albino rats were used: First group consisted
of healthy controls; the second group included the
untreated STZ-diabetics; 30 days of irbesartan or perindopril
treated STZ-diabetics formed the third and the fourth
groups, respectively; while the subjects receiving a combined
treatment with irbesartan and perindopril for 30 days
consisted the fifth group. TUNEL method for apoptosis and
immunohistochemical staining for TGF-b1, a-SMA, clusterin-
b and clusterin-a/b antibodies were performed.
Apoptotic cells especially increased in the kidney tubuli of
untreated diabetic group and on the contrary, a significant
decrease was observed in the group that received a combined
drug treatment. While sCLU was increased in the
glomeruli and tubuli of the untreated diabetic group, it was
decreased in all the treated groups. An increase in the
nCLU immunoreactivity was observed in the podocytes,
mesangial cells, and the injured tubule cells of the
untreated diabetic group. nCLU immunopositive cells were
decreased in all treated diabetic groups. In addition to this,
the distribution of nCLU was similar to the distribution of
apoptotic cells in the diabetic groups. Our results indicate
that sCLU expression in diabetic nephropathy was induced
due to renal tissue damage, and the nCLU expression
increase in renal tubuli was related to apoptosis. Although
irbesartan and perindopril prevented further renal injury in
diabetes, a combined application of low-dose ACEI and
AT1R blockers revealed more efficient measures, by means
of renal damage prevention.