Bekir Uğur ERGÜR, H. Alper BAĞRIYANIK, Ülker SÖNMEZ, Ali Rıza ŞİŞMAN, Nükhet TUĞYAN, Zişan BULDAN

İskemi-reperfüzyon modelinde, böbrek korteksindeki histopatolojik değişiklikler ve eritropoetinin koruyucu etkisi

Amaç: Eritropoetin (Epo), böbrekten salgılanan glikoprotein yapıda ve hematopoetik sistem üzerine etkili bir hormondur. Son yıllarda yapılan araştırmalarda, Epo'nun santral sinir sistemi hücrelerini iskemik hasara karşı koruduğu bulunmuştur. Biz de araştırmamızda, böbrek dokusunda iskemi-reperfüzyon (I/R) hasarının oluşturduğu histopatolojik değişiklikler ve Epo'nun koruyucu etkisini deneysel bir model üzerinde araştırdık. Gereç ve yöntem: Bu çalışmada, 21 adet 200-250 g Wistar Albino susu sıçan kullanıldı. Kullanılan sıcak iskemi modelinde, 1 saat iskemi, 30 dakika reperfüzyon uygulandı. I/R hasarına karşı koruyucu ajan olarak reperfüzyon öncesi intra-peritoneal (i.p.) 25 IU/kg ve 100 IU/kg Epo kullanıldı. İskemi sonrası böbreklerdeki histopatolojik değişiklikler ışık mikroskobunda değerlendirildi. Bulgular: Elde edilen kesitlerin mikroskopik incelemesinde, Epo 100 IU/kg verilen grupta, intertisyel eritrosit ekstravazasyonunun, proksimal tubul hücrelerinde vakuolizasyonun, mononükleer hücre infiltrasyonunun en aza indiği gözlenmiştir. Sonuç: Çalışmamızda Epo'nun doza bağlı olarak böbrek I/R haşatını önlediğini gördük. Koruyucu ajan olarak. Epo'nun, oluşan böbrek hasarına karşı yeni bir sağaltım yöntemi olabileceği düşüncesindeyiz.

Anahtar Kelimeler:

Böbrek korteksi, Reperfüzyon hasarı, Sıçan, Wistar, Modeller, hayvan, Eritropoietin, Modeller, teorik

The histopathological changes in the kidney kortex in an ischemia-reperfusion model and erythropoietin protective effect

Erythropoietin (Epo) is a glycoprotein influence on the heamatopoetic system and is secceted from kidney. In the recent studies, the protective effect of Epo on central nerve system cells against ischemia-reperfusion (I/R) injury was found. We aimed to observe die histopathological changes in I/R injury in the kidney and the protective role of Epo in an experimental model. Material and method: In this study, 21 male 200-250 gr Wistar rats were used. 1 hour ischemia and 30 minutes reperfusion was maintained in the model used. Epo was given 25 IU/kg and 100 IU/kg intraperitoneally as a protective agent against I/R injury. The kidney tissue specimens were examined and scored under light microscope. Results: In Epo 100 IU/kg group, mononuclear cell infiltrations, vacuolations in proximal tubules and intertitial erythrocyte extravasations were significantly decreased.Conclusion: We observe with these findings that Epo protects kidney from I/R injury according; to its dose. We think, Epo might be a new protective agent against I/R injury

Keywords:

Kidney Cortex, Reperfusion Injury, Rats, Wistar, Models, Animal, Erythropoietin, Models, Theoretical,

___

1. Grace PA, Ischemia-reperfusion injury. Br J Surg 1994;81:637-647.
2. Ergün O, Ulman C, Kılıçalp AS. Carnitine as a agent in experimental renal ischemia-reperfusion injury. Urol Res 2001;29:186-189.
3. Joel MW. The cell biology of ischemic renal injury. Kid Int 1991;39:476-500.
4. Rhoden EL, Luitz PL, Claudio RR et al. Role of the L-arginin/nitric oxide pathway in renal ischemia-reperfusion in rats. Eur J Surg 2001;167:224-228.
5. Weight SC, Furness PN, Nicholson ML. Biphasic role for nitric oxide in experimental warm ischemia-reperfusion injury. Br J Surg 1999;86:1039-1046.
6. Francis BG. Effects of nitric oxide synthase blockers on renal function. Nephrol Dial Transplant 2001;16:10-13.
7. Pandit JJ, Maxwell PH. New insights into the regulation of erytrhropoietin production, Br J Anaesthesia 2000;85:329-330.
8. Calapai G, Marciano MC, Corica F et al. Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation. Eur J Pharm 2000; 401:349-356.
9. Chin K, Yu X, Besleslin-Cokic B, et al. Production and processing of erythropoietin receptor transcripts in brain. Molecular Brain Research 2000;81:29-42.
10. Eckkardt KU. After 15 jrears of success-perspectives of erythropoietin therapy. Nephrol Dial Transplant 2001;16:1745-1749.
11. Gustavo M, Luis HT, Stuart B et al. Nitric oxide diminishes apoptosis and p53 gene expression after renal ischemia-reperfusion injury. Transplant 2000;70: 1431-1437.
12. Özen S, Usta Y, Şahin I et al. Assosiation of nitric oxide production and apoptosis in a model of experimental nephropaty. Nephrol Dial Transplant 2001;16:32-38.
13. Daniel AS, Yining X, Nestor F et al. Nitric oxide synthase activity in renal ischemia-reperfusion injury in the rat. Transplantation 1997;63:495-500.
14. Tan Chorh C, Tan Lay FI, Eckardt K. Erythropoietin production in rats with post-ischemic acute renal failure. Kid Int 1996;50:1958-1964.
15. Sang KJ, Su YY, Kyung HC et al. Alfa-msh decreases apoptosis in ischemic acute renal failure in rats; possible mechanism of this beneficial effect. Nephrol Dial Transplant 2001;16:1583-1591.
16. Kelly KJ, Nancy R, Green AL. Induction of stress response proteins and experimental renal ische-mi/reperfusion. Kid Int 2001; 59:1798-1802.
17. Koji H, Kenji O, Yuji T et al. Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg 2000;232: 272-280.
18. Michael Ross. Histology, A text and Atlas. 3rd Edition Oxford Publications 1995;558-567.
19. Garcia-Crıado FJ, Eleno N, Santos-Benito F et al. Protective effect of exogenous nitric oxide on the renal function and inflamatory response in a model of ischemia-reperfusion. Transplant 1998;66:982-990.
20. Hsı C, Yukımasa K, Leonard C. Alfa- melanocyte stimulating hormone inhibits renal injury in the absence of neutrophils. Kid Int 1998;54:765-774.
21. Masahiro S, Tong-Chun W. In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci 1998;95:4635-4640.
22. Anagnostou A, Lee ES, Kessimian N et al. Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci 1994;91:3974-3978.