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Deneysel Diyabetik Nefropatide İrbesartan’ın Apoptoz Üzerine Koruyucu Etkileri

Protective effects of irbesartan on apoptosis in experimental diabetic nephropathy

Journal Name:

  • Cerrahpaşa Tıp Dergisi

Publication Year:

  • 2009

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
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.
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Abstract (Original Language): 
Amaç: Bu çalışmada, Angiotensin II tip 1 reseptör blokeri olan irbesartan’ın Streptozotocin (STZ)-diyabetik sıçanlarda apoptoz ve apoptozu düzenleyen antiapoptotik (Bcl-2) proteini üzerine etkileri araştırıldı. Yöntem: Çalışmada 24 adet erkek Wistar tipi albino sıçandan oluşan 3 grup kullanıldı. 1.grup; sağlıklı 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 sıçan grubu olarak düzenlendi. Deney süresince tüm gruplardaki sıçanların kan glukoz ve mikroalbuminüri düzeyleri ölçüldü. Deney sonunda alınan böbrek dokuları nötral formalde tespit edilip parafine gömüldü. Böbrek doku kesitlerine apoptoz tespiti amacıyla TUNEL metodu uygulandı. Bcl-2 antikoru kullanılarak immunohistokimyasal boyama yapıldı. Bulgular: İrbesartan uygulanan diyabetik grupta mikroalbuminüri düzeyleri tedavisiz diyabetik grupa kıyasla anlamlı olarak azaldı (p<0,001). Tedavisiz STZ-diyabetik grupta tubullerde yaygın apoptotik hücreler tespit edilirken (p<0.01), Bcl-2 immun reaktivitesinde azalma gözlendi. İrbesartan uygulanan diyabetik grupta, diyabetik grup ile kıyaslandığında apoptotik hücrelerin sayısında azalma görülürken, antiapoptotik Bcl-2 immun reaktivitesinin kontrol gruba yakın olduğu gözlendi. Sonuç: STZ-diyabeti ile oluşturulan nefropatide, AT1 reseptör blokeri irbesartan uygulamasının renoprotektif etkiye neden olduğu, Ang II aracılı apoptoz artışını engelleyebileceği sonucuna varıldı.
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  • 2
15-22
  • Turkish

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