Deneysel diyabetik nefropatide ırbesartan'ın apoptoz üzerine koruyucu etkileri

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. I.grup; sağlıklı kontrol, 2.grup; tedavisiz STZ-diyabetik(60 mg/kg, tek doz, i.p), 3-grup; irbesartan(15 mg/kg/gün, intragastric 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 TÜNEL metodu uygulandı. Bcl-2 antikoru kullanılarak immunohistokimyasal boyama yapıldı. Bulgular: İrbesartan uygulanan diyabetik grupta mikroalbuminüri düzeyleri tedavisiz diyabetik grupa kıyasla anlamlı olarak azaldı (p

Protective effects of irbesartan on apoptosis in experimental diabetic nephropathy

Objectives: The aim of this study is to investigate effects of irbesartan as an Ang II type I 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 apopto¬sis 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 dia¬betic group (p

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  • 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,Valdes F, Pasaro E, Diaz 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, Dıvjak M, et al. Altered signalling and regulatory mechanisms of apoptosis in focal and segmental glomerulosclerosis. J Am Soc Nephrol 2001; 12: 1422-1433.
  • 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 cas-pases 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 Yılmazer, M Öztürk. Işık Mikroskopide İmmünoişaretleme Yöntemleri. Uygulamalı Ultrastruktürel İmmunohistokimya Kurs Kitapçığı. İstanbul, 6-8 Mayıs 1998; 48-74.
  • 13.Tunçdemir M, Öztürk 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 streptozo-tocin-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.