Buradasınız

Anasayfa » Content

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.
Bookmark/Search this post with
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.
FULL TEXT (PDF): 
PDF icon arastirmax-deneysel-diyabetik-nefropatide-irbesartanin-apoptoz-uzerine-koruyucu-etkileri.pdf
  • 2
15-22
  • Turkish

REFERENCES

References: 

Kaynaklar
1. Antus B, Mucsi I, Rosivall L. Apoptosis induction and
inhibition of cellular proliferation by angiotensin II:
possible implication and perspectives. Acta
Physiologica Hungarica 2000; 87: 5-24.
2- Valdés F, Pásaro E, Díaz I, et al. Segmental heterogeneity
in Bcl-2, Bcl-xL and Bax expression in rat
tubular epithelium after ischemia-reperfusion.
Nephrology (Carlton) 2008; 13: 294-301.
3. El Nahas AM. Plasticity of kidney cells: role in kidney
remodeling and scarring. Kidney Int 2003; 64: 1553-
1563.
4. Wang VY, Tzanidis A, D›vjak M, et al. Altered signalling
and regulatory mechanisms of apoptosis in
focal and segmental glomerulosclerosis. J Am Soc
Nephrol 2001; 12: 1422-1433.
Cerrahpafla T›p Derg 2009; 40(1): 15-22
5. Ruiz-Ortega M, Lorenzo O, Ruperez M, et al. Role of
the renin-angiotensin system in vascular diseases:
expanding the field. Hypertension 2001; 38: 1382-
1387.
6. Ding G, Reddy K, Kapasi AA, et al. Angiotensin II
induces apoptosis in rat glomerular epithelial cells.
Am J Physiol Renal Physiol 2002; 283: 173-180.
7. Ruilope LM. Renoprotection and renin-anjiotensin system
blockade in diabetes mellitus. Am J Hypertension
1997; 10: 325-331.
8. Kalender B, Öztürk M, Tunçdemir M, et al.
Renoprotective effects of valsartan and enalapril in
STZ-induced diabetes in rats. Acta Histochem 2002;
104: 123-130.
9. Wong VY, Keller PM, Nuttall ME, et al. Role of caspases
in human renal proximal tubular epithelial cell
apoptosis. Eur J Pharm 2001; 433: 135-140.
10. Ortiz A, Justo P, Sanz A, et al. Targeting apoptosis in
acute tubular injury. Biochem Pharmacol 2003; 66:
1589-1594.
11. Makino H, Sugiyama H, Kashihara N. Apoptosis and
extracellular matrix-cell interactions in kidney disease.
Kidney Int Suppl 2000; 77: 67-75.
12. Öztürk M. Editörler: S Y›lmazer, M Öztürk. Ifl›k
Mikroskopide ‹mmünoiflaretleme Yöntemleri.
Uygulamal› Ultrastruktürel ‹mmunohistokimya Kurs
Kitapc›¤›. ‹stanbul, 6-8 May›s 1998; 48-74.
13. Tunçdemir M, Özturk M. The effects of ACE inhibitor
and angiotensin receptor blocker on clusterin and
apoptosis in the kidney tissue of streptozotocin-diabetic
rats. J Mol Histol 2008; 39: 605-616.
14. UNISTAT 5.0 (C.T.F. Biyoistatistik) ®)
15. Bamri-Ezzine S, Ao ZJ, Londono I, et al. Apoptosis of
tubular epithelial cells in glycogen nephrosis during
diabetes. Lab Invest 2003; 83: 1069-1080.
16. Zhang G, Khanna P, Chan LL, et al. Diabetes-induced
apoptosis in rat kidney. Biochem Mol Med 1997; 61:
58-62.
17. Kumar D, Zimpelmann J, Robertson S, Burns KD.
Tubular and interstitial cell apoptosis in the streptozotocin-
diabetic rat kidney. Nephron Exp Nephrol 2004;
96: 77-88.
18. Kelly DJ, Cox AJ, Tolcos M, et al. Attenuation of tubular
apoptosis by blockade of the renin-angiotensin system
in diabetic Ren-2 rats. Kidney Int 2002; 61: 31-39.
19. Ortiz A, Ziyadeh FN, Neilson EG. Expression of apoptosis-
regulatory genes in renal proximal tubular epithelial
cells exposed to high ambient glucose and in diabetic
kidneys. J Investig Med 1997; 45: 50-56.
20. Cao Z, Kelly DJ, Cox A, et al. Angiotensin type 2
receptor is expressed in the adult rat kidney and promotes
cellular proliferation and apoptosis. Kindney Int
2000; 58: 2437-2451.
21. Zhang G. Role of apoptosis and Bcl-2/Bax in the
development of tubulointerstitial fibrozis during experimental
obstructive nephropathy. Exp Nephrol 2001;
9: 71-80.
22

Thank you for copying data from http://www.arastirmax.com