Deneysel diyabetik nefropatide irbesartan’ın apoptoz üzerine koruyucu etkileri


Tunçdemir M. , Öztürk M.

Cerrahpaşa Tıp Dergisi, cilt.40, ss.15-22, 2009 (Hakemli Üniversite Dergisi)

  • Cilt numarası: 40 Konu: 1
  • Basım Tarihi: 2009
  • Dergi Adı: Cerrahpaşa Tıp Dergisi
  • Sayfa Sayıları: ss.15-22

Özet

Amaç: Bu çal›?mada, Angiotensin II tip 1 reseptör blokeri olan irbesartan’›n Streptozotocin (STZ)-diyabetik s›çanlarda apoptoz ve apoptozu

düzenleyen antiapoptotik (Bcl-2) proteini üzerine etkileri ara?t›r›ld›. 
Yöntem: Çal›?mada 24 adet erkek Wistar tipi albino s›çandan olu?an 3 grup kullan›ld›. 1.grup; sa¤l›kl› kontrol, 2.grup; tedavisiz STZ-diyabetik (60 mg/kg, tek doz, i.p), 3.grup; irbesartan (15 mg/kg/gün, intragastrik, 4 hafta) uygulanan STZ-diyabetik s›çan grubu olarak düzenlendi. Deney süresince tüm gruplardaki s›çanlar›n kan glukoz ve mikroalbuminüri düzeyleri ölçüldü. Deney sonunda al›nan böbrek dokular›
nötral formalde tespit edilip parafine gömüldü. Böbrek doku kesitlerine apoptoz tespiti amac›yla TUNEL metodu uyguland›. Bcl-2 antikoru
kullan›larak immunohistokimyasal boyama yap›ld›. 
Bulgular: ‹rbesartan uygulanan diyabetik grupta mikroalbuminüri düzeyleri tedavisiz diyabetik grupa k›yasla anlaml› olarak azald› (p<0,001).
Tedavisiz STZ-diyabetik grupta tubullerde yayg›n apoptotik hücreler tespit edilirken (p<0.01), Bcl-2 immun reaktivitesinde azalma gözlendi. ‹rbesartan uygulanan diyabetik grupta, diyabetik grup ile k›yasland›¤›nda apoptotik hücrelerin say›s›nda azalma görülürken, antiapoptotik Bcl-2 immun reaktivitesinin kontrol gruba yak›n oldu¤u gözlendi. 
Sonuç: STZ-diyabeti ile olu?turulan nefropatide, AT1 reseptör blokeri irbesartan uygulamas›n›n renoprotektif etkiye neden oldu¤u, Ang II
arac›l› apoptoz art›?›n› engelleyebilece¤i sonucuna var›ld›.

 

Objectives: The aim of this study is to investigate effects of irbesartan as an Ang II type 1 blocker on apoptosis and anti-apoptotic protein
Bcl-2 in the streptozotocin (STZ)-induced diabetic rat.
Methods: 24 male Wistar albino rats were used for three groups. The first group was the non-diabetic control group. Second group was the
untreated STZ-induced diabetic group, (60 mg/kg, single dose, i.p). The third group was irbesartan treated (15 mg/kg/day, intragastric, for 4
week) STZ-diabetic rats. During the period of the experiment, blood glucose and microalbuminuria levels of the rats were measured. At the
end of the study renal tissue samples were fixed in neutral formalin and embedded in paraffin. Tissue sections were examined for apoptosis by TUNEL method and for anti-apoptotic protein Bcl-2 by immunohistochemical staining.
Results: The microalbuminuria levels of the irbesartan treated diabetic group were found reduced when compared with the untreated diabetic group (p<0,001). Widespread apoptosis was seen in the tubules of untreated diabetic group (p<0,01) and a decrease in the immunoreactivity of Bcl-2 were observed in glomeruli of the diabetic group. In the irbesartan treated diabetic group, antiapoptotic Bcl-2 immunoreactivity was similar to the results obtained from the control group and a decrease the number of apoptotic cells were observed.
Conclusion: The results suggested that irbesartan treatment has renoprotective effects in STZ-diabetic nephropathy. AT1 receptor blockade
inhibites Ang II mediated apoptosis in the STZ-diabetic nephropathy.