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Deneysel Hipertansiyon ve Diyabet Modeli Oluşturulan Sıçanlarda Böbreğin İmmunohistokimyasal Olarak İncelenmesi,

Yıl 2012, Cilt: 26 Sayı: 2, 91 - 101, 01.08.2012

S.cilaker Mıcılı B.uğur Ergür C. Özoğul S. Sarıoğlu A. Bağrıyanık K. Tuğyan Ç. Pekçetin Ü. Sönmez İ. Tekmen G. Erbil G. Güner Akdoğan D. Özyurt Z. Buldan

Öz

Anahtar Kelimeler

-

Kaynakça

  • 1. Bağrıaçık N. Diabetes Mellitus: Tanımı, Tarihçesi, Sınıf- laması ve Sıklığı, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri, Diyabetes Mellitus Sempozyumu, 9-18, 1997, İstanbul
  • 2. Araz M. Diabetes Mellitus. In: Sağlıker Y, Ed. İç Hastalıkları Prensipleri, 4. Baskı. Nobel Tıp Kitabevi, İstanbul, 2004; p. 2109-2123.
  • 3. Nolan CR, Schrier RW. Kidney in hypertension. In: Schrier RW editor. Renal and Electrolyte Disorders.6th edition. Lippincott Williams&Wilkins, 2005;272-324.
  • 4. Williams B. Epidemiology and pathogenesis of hypertension in people with Diabetes Mellitus. In: Bryan Williams ed. Hypertension in diyabetes. First Edition, London, Newyork, Martin Dunitz 2003;3-24.
  • 5. Parlakpınar H, Yanılmaz M, Ağlamış S, Acet A. Kardiyovasküler sistem ve anjiyotensin II tip 2 reseptörü (AT2). İnönü Üniversitesi Tıp Fakültesi Dergisi 2004;11:49-52.
  • 6. Neufeld G, CohenT, Gengrınovıtch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. The Faseb 1999;13:9-22.
  • 7. Poltorak Z, Cohen T, Sivan R, et al. VEGF145 a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem 1997; 272;7151-58.
  • 8. Khimji A, Rockey DC. Endothelin-Biology and disease. Cell Signal 2010; 22:1615-625.
  • 9. Benigni A, Perıco N, Gasparı F, Zoja C. Increased renal endothelin production in rats with reduced renal mass Am J Physiol 1991;29: 331-339.
  • 10. Masharani U. Diabetes Mellitus&Hypoglisemia. In: Mcphee SJ, Papadakis MA editors. Current Medical Diagnosis&Treatment. Forty-Eighth Editions. Newyork, McGraw Hill Medical 2009;1053-1094.
  • 11. Jenette JC, Olson JL, Schwartz MM, Silva FG. Heptinstall's pathology of the kidney. 5th edition. Philadelphia. Lippincott-Raven 1998;2:943-1002.
  • 12. Alpha-lipoic acid. Alternative Medicine Review 2006; 11:232-237.
  • 13. Snell EE, Strong FM, Peterson WH. Growth factos for bacteria. VI.Fractionation and properties of an accessory factor for actic acid bacteria. Biochem J 1937;31:1789.
  • 14. Reed LJ, Gunsalus IC, Schnakenberg GHF, et al. Isolation, characterization and structure of α-lipoic acid. Jacs 1953;75:1267-1277.
  • 15. Eguíluz Lumbreras P, Hernández AP, Gómez Zancajo VR, et al. Nephrectomy in polycystic kidney disease before transplantation. Archivos Espanoles de Urologia 2010;63:403-409.
  • 16. Shore I, Moss J. Electronmicroscopy in diagnostic renal pathology Current Diagnostic Pathology 2002;8:207-215.
  • 17. E. Guneli, K. Tugyan, H. Ozturk, M. Gumustekin, S. Cilaker, N. Uysal. Effect of Melatonin on Testicular Damage in Streptozotocin-Induced Diyabetes Rats. Eur Surg Res 2008; 26: 354-360.
  • 18. Guray S, Sarıoglu M, Turkmen O, et al. Cyclosporine A Toxicity in Association With Reduced Renal Mass. M. Transplantation Proceedings 2003; 35:3128–3133.
  • 19. Cakatay U, Kayali R, Kiziler AR, Aydemir B. Postmitotic tissue selenium and manganese levels in alpha-lipoic acid-supplemented aged rats. Chemico-Biological Interactions 2008;171: 306–311.
  • 20. Williams B. Epidemiology and pathogenesis of hypertension in people with Diabetes Mellitus. In: Bryan Williams ed. Hypertension in diyabetes. First Edition, London, Newyork, Martin Dunitz. 2003;3-24.
  • 21. Taal MW, Brenner BM. Evolving strategies for renoprotection: non-diabetic chronic renal disease. Current Opinion in Nephrology and Hypertension 2001; 10:523- 531.
  • 22. Maritim AC, Sanders RA, Watkins JB. Effects of α-lipoic acid on biomarkers of oxidative stress in streptozotocininduced diabetic rats. Journal of Nutritional Biochemistry 2003;14: 288–294.
  • 23. Özkan Y, Yılmaz Ö, Öztürk A, Erşan Y. Effects of triple antioxidant combination (vitamin E, vitamin C and alipoic acid) with insulin on lipid and cholesterol levels and fatty acid composition of brain tissue in experimental diabetic and non-diabetic rats. Cell Biology International 2005; 29: 754-760.
  • 24. Cohuet G, Struijker-Boudier H. Mechanisms of target organ damage caused by hypertension: Therapeutic potential. Pharmacology & Therapeutics 2006;111:81-98.
  • 25. Vasdev S, Gill V, Parai S, Gadag V. Dietary lipoic acid supplementation attenuates hypertension in Dahl salt sensitive rats. Molecular and Cellular Biochemistry 2005;275: 135-141.
  • 26. Vasdev S, Ford CA, Parai S, Longerich L, Gadag V. Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. J Hypertens 2000; 18: 567- 573.
  • 27. Zimpelmann J, Kumar D, Levine DZ, Wehbi G. Early Diabetes Mellitus stimulates proximal tubule renin mRNA expression in the rat. Kidney International. 2000; 2320-30.
  • 28. Mezzano S, Droguett A, Burgos ME, Ardiles LG, Flores CA, Aros CA et al. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney International, 2003;64: 64-70.
  • 29. Hsieh TJ, Zhang SL, Filep JG, et al. High Glucose Stimulates Angiotensinogen Gene Expression via Reactive Oxygen Species Generation in Rat Kidney Proximal Tubular Cells. Endocrinology 2002;143:2975-2985.
  • 30. Cao Z, Bonnet F, Candido R, et al. Angiotensin type 2 receptor antagonism confers renal protection in a rat model of progressive renal ınjury J Am Soc Nephrol 2002;13: 1773-1787.
  • 31. Cooper M, Vranes D, Youssef S, et al. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR- 2 in experimental diyabetes. Diyabetes 1999; 48: 2229–2239.
  • 32. Braun L, Kardon T, Reisz-Porszasz Z, Banhegy G. The regulation of the induction of vascular endothelial growth factor at the onset of diyabetes in spontaneously diabetic rats. Life Sciences 2001;69:2533-2542.
  • 33. Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 2007; 96:1788-1795.
  • 34. Kelly D, Hepper C, Wu LL, Cox AJ, Gilbert RE. Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model Nephrol Dial Transplant 2003;18: 1286-1292
  • 35. Sorakin A, Kohan DE. Physiology and pathology of endothelin-1 in renal mesangium. Am J Physiol Renal Physiol 2003; 285:579-589.
  • 36. Chen HC, Guh JH, Shin SJ, Tsai JH. Reactive oxygen species enhances endothelin-1 production of diabetic rat glomeruli in vitro and in vivo. J Lab Clin Med 2000;309- 315.
  • 37. Vierhapper H, Wagner O, Nowotny P, Waldhausl W. Effect of endothelin-1 in man. Circulation 1990;81: 1415.
  • 38. Rubinstein I. Prolonged Anti-Hypertensive Effects of Oral Sitaxsentan, a Selective ETA Endothelin Receptor Antagonist, in Spontaneoulsy Hypertensive Hamsters Cardiovasc. Drugs Ther. 2006;20:387.
  • 39. Lariviere R, Lebel M. Endothelin-1 in chronic renal failure and hypertension. Can J Physiol Pharmacol 2003; 81: 607–621.

Deneysel Hipertansiyon ve Diyabet Modeli Oluşturulan Sıçanlarda Böbreğin İmmunohistokimyasal Olarak İncelenmesi,

Yıl 2012, Cilt: 26 Sayı: 2, 91 - 101, 01.08.2012

S.cilaker Mıcılı B.uğur Ergür C. Özoğul S. Sarıoğlu A. Bağrıyanık K. Tuğyan Ç. Pekçetin Ü. Sönmez İ. Tekmen G. Erbil G. Güner Akdoğan D. Özyurt Z. Buldan

Öz

Amaç: Bu çalışmada, deneysel olarak ayrı ayrı ve birlikte diyabet ve hipertansiyon modeli oluşturulan sıçanlarda, lipoik asidin hipertansif ve diyabetik böbrek üzerindeki tedavi edici/hasar önleyici etkisinin araştırılması amaçlandı. Yöntemler: Çalışmamızda Wistar cinsi ratlar 8 gruba ayrıldı (n=7). I. grup; Kontrol, II. Grup; Diabetes Mellitus, III. grup; 5/6 Nefrektomi, IV. Grup; Lipoik asit, V. Grup; 5/6 Nefrektomi+Diyabet, VI. grup, Diyabet+Lipoik asit VII. Grup; 5/6 Nefrektomi+Lipoik asit ve VIII. Grup; 5/6Nefrektomi+Diyabet+Lipoik asit. Diyabet modeli 45 mg/kg STZ enjeksiyonu ile oluşturuldu ve hipertansiyon modeli için 5/6 nefrektomi modeli uygulandı. dl-α-Lipoik asit 30mg/kg/gün olacak şekilde 8 hafta oral gavaj yöntemi ile deneklere uygulandı. Böbrek dokuları rutin ışık mikroskobik doku takip işlemlerinden geçirilip parafin bloklara gömüldü. İmmünohistokimyasal olarak AT1 (Anjiyotensin II tip I reseptörü), VEGF (Vasküler Endotelial Büyüme Faktörü) ve ET1 (Endotelin 1) antikorları işaretlendi. Bulgular: Diyabet ve nefrektomi modellerinin ayrı ayrı ve birlikte uygulandığı deneysel gruplarda (Grup 2,3,5), glomerüloskleroz, mononükleer hücre infiltrasyonu, intersitisiyel fibrozis, damarlarda ve tübüllerde dilatasyon ve hiyalin materyal birikimi ile tübüler yapıların dejenerasyonu gözlendi. Aynı gruplarda tübülointersitisiyel ve glomerüler AT1 azalırken, VEGF ve ET1 artış göstermişti. Lipoik asit tedavi gruplarında ise AT1’de artış, VEGF ve ET1’de ise Kontrol ve Lipoik asit grubuna benzer şekilde azalma gözlendi. Sonuç: Diyabet ve hipertansiyonun birlikte gözlenmesinin böbrek hasarının hızlı ilerlemesine neden olduğu, lipoik asidin bu hastalıklara karşı böbrek üzerinde tedavi edici etkisinin olduğu sonucuna varıldı

Anahtar Kelimeler

Böbrek diyabet hipertansiyon immunohistokimya lipoik asit

Kaynakça

  • 1. Bağrıaçık N. Diabetes Mellitus: Tanımı, Tarihçesi, Sınıf- laması ve Sıklığı, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri, Diyabetes Mellitus Sempozyumu, 9-18, 1997, İstanbul
  • 2. Araz M. Diabetes Mellitus. In: Sağlıker Y, Ed. İç Hastalıkları Prensipleri, 4. Baskı. Nobel Tıp Kitabevi, İstanbul, 2004; p. 2109-2123.
  • 3. Nolan CR, Schrier RW. Kidney in hypertension. In: Schrier RW editor. Renal and Electrolyte Disorders.6th edition. Lippincott Williams&Wilkins, 2005;272-324.
  • 4. Williams B. Epidemiology and pathogenesis of hypertension in people with Diabetes Mellitus. In: Bryan Williams ed. Hypertension in diyabetes. First Edition, London, Newyork, Martin Dunitz 2003;3-24.
  • 5. Parlakpınar H, Yanılmaz M, Ağlamış S, Acet A. Kardiyovasküler sistem ve anjiyotensin II tip 2 reseptörü (AT2). İnönü Üniversitesi Tıp Fakültesi Dergisi 2004;11:49-52.
  • 6. Neufeld G, CohenT, Gengrınovıtch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. The Faseb 1999;13:9-22.
  • 7. Poltorak Z, Cohen T, Sivan R, et al. VEGF145 a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem 1997; 272;7151-58.
  • 8. Khimji A, Rockey DC. Endothelin-Biology and disease. Cell Signal 2010; 22:1615-625.
  • 9. Benigni A, Perıco N, Gasparı F, Zoja C. Increased renal endothelin production in rats with reduced renal mass Am J Physiol 1991;29: 331-339.
  • 10. Masharani U. Diabetes Mellitus&Hypoglisemia. In: Mcphee SJ, Papadakis MA editors. Current Medical Diagnosis&Treatment. Forty-Eighth Editions. Newyork, McGraw Hill Medical 2009;1053-1094.
  • 11. Jenette JC, Olson JL, Schwartz MM, Silva FG. Heptinstall's pathology of the kidney. 5th edition. Philadelphia. Lippincott-Raven 1998;2:943-1002.
  • 12. Alpha-lipoic acid. Alternative Medicine Review 2006; 11:232-237.
  • 13. Snell EE, Strong FM, Peterson WH. Growth factos for bacteria. VI.Fractionation and properties of an accessory factor for actic acid bacteria. Biochem J 1937;31:1789.
  • 14. Reed LJ, Gunsalus IC, Schnakenberg GHF, et al. Isolation, characterization and structure of α-lipoic acid. Jacs 1953;75:1267-1277.
  • 15. Eguíluz Lumbreras P, Hernández AP, Gómez Zancajo VR, et al. Nephrectomy in polycystic kidney disease before transplantation. Archivos Espanoles de Urologia 2010;63:403-409.
  • 16. Shore I, Moss J. Electronmicroscopy in diagnostic renal pathology Current Diagnostic Pathology 2002;8:207-215.
  • 17. E. Guneli, K. Tugyan, H. Ozturk, M. Gumustekin, S. Cilaker, N. Uysal. Effect of Melatonin on Testicular Damage in Streptozotocin-Induced Diyabetes Rats. Eur Surg Res 2008; 26: 354-360.
  • 18. Guray S, Sarıoglu M, Turkmen O, et al. Cyclosporine A Toxicity in Association With Reduced Renal Mass. M. Transplantation Proceedings 2003; 35:3128–3133.
  • 19. Cakatay U, Kayali R, Kiziler AR, Aydemir B. Postmitotic tissue selenium and manganese levels in alpha-lipoic acid-supplemented aged rats. Chemico-Biological Interactions 2008;171: 306–311.
  • 20. Williams B. Epidemiology and pathogenesis of hypertension in people with Diabetes Mellitus. In: Bryan Williams ed. Hypertension in diyabetes. First Edition, London, Newyork, Martin Dunitz. 2003;3-24.
  • 21. Taal MW, Brenner BM. Evolving strategies for renoprotection: non-diabetic chronic renal disease. Current Opinion in Nephrology and Hypertension 2001; 10:523- 531.
  • 22. Maritim AC, Sanders RA, Watkins JB. Effects of α-lipoic acid on biomarkers of oxidative stress in streptozotocininduced diabetic rats. Journal of Nutritional Biochemistry 2003;14: 288–294.
  • 23. Özkan Y, Yılmaz Ö, Öztürk A, Erşan Y. Effects of triple antioxidant combination (vitamin E, vitamin C and alipoic acid) with insulin on lipid and cholesterol levels and fatty acid composition of brain tissue in experimental diabetic and non-diabetic rats. Cell Biology International 2005; 29: 754-760.
  • 24. Cohuet G, Struijker-Boudier H. Mechanisms of target organ damage caused by hypertension: Therapeutic potential. Pharmacology & Therapeutics 2006;111:81-98.
  • 25. Vasdev S, Gill V, Parai S, Gadag V. Dietary lipoic acid supplementation attenuates hypertension in Dahl salt sensitive rats. Molecular and Cellular Biochemistry 2005;275: 135-141.
  • 26. Vasdev S, Ford CA, Parai S, Longerich L, Gadag V. Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. J Hypertens 2000; 18: 567- 573.
  • 27. Zimpelmann J, Kumar D, Levine DZ, Wehbi G. Early Diabetes Mellitus stimulates proximal tubule renin mRNA expression in the rat. Kidney International. 2000; 2320-30.
  • 28. Mezzano S, Droguett A, Burgos ME, Ardiles LG, Flores CA, Aros CA et al. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney International, 2003;64: 64-70.
  • 29. Hsieh TJ, Zhang SL, Filep JG, et al. High Glucose Stimulates Angiotensinogen Gene Expression via Reactive Oxygen Species Generation in Rat Kidney Proximal Tubular Cells. Endocrinology 2002;143:2975-2985.
  • 30. Cao Z, Bonnet F, Candido R, et al. Angiotensin type 2 receptor antagonism confers renal protection in a rat model of progressive renal ınjury J Am Soc Nephrol 2002;13: 1773-1787.
  • 31. Cooper M, Vranes D, Youssef S, et al. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR- 2 in experimental diyabetes. Diyabetes 1999; 48: 2229–2239.
  • 32. Braun L, Kardon T, Reisz-Porszasz Z, Banhegy G. The regulation of the induction of vascular endothelial growth factor at the onset of diyabetes in spontaneously diabetic rats. Life Sciences 2001;69:2533-2542.
  • 33. Kamba T, McDonald DM. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 2007; 96:1788-1795.
  • 34. Kelly D, Hepper C, Wu LL, Cox AJ, Gilbert RE. Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model Nephrol Dial Transplant 2003;18: 1286-1292
  • 35. Sorakin A, Kohan DE. Physiology and pathology of endothelin-1 in renal mesangium. Am J Physiol Renal Physiol 2003; 285:579-589.
  • 36. Chen HC, Guh JH, Shin SJ, Tsai JH. Reactive oxygen species enhances endothelin-1 production of diabetic rat glomeruli in vitro and in vivo. J Lab Clin Med 2000;309- 315.
  • 37. Vierhapper H, Wagner O, Nowotny P, Waldhausl W. Effect of endothelin-1 in man. Circulation 1990;81: 1415.
  • 38. Rubinstein I. Prolonged Anti-Hypertensive Effects of Oral Sitaxsentan, a Selective ETA Endothelin Receptor Antagonist, in Spontaneoulsy Hypertensive Hamsters Cardiovasc. Drugs Ther. 2006;20:387.
  • 39. Lariviere R, Lebel M. Endothelin-1 in chronic renal failure and hypertension. Can J Physiol Pharmacol 2003; 81: 607–621.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler
Yazarlar

S.cilaker Mıcılı Bu kişi benim

B.uğur Ergür Bu kişi benim

C. Özoğul Bu kişi benim

S. Sarıoğlu Bu kişi benim

A. Bağrıyanık Bu kişi benim

K. Tuğyan Bu kişi benim

Ç. Pekçetin Bu kişi benim

Ü. Sönmez Bu kişi benim

İ. Tekmen Bu kişi benim

G. Erbil Bu kişi benim

G. Güner Akdoğan Bu kişi benim

D. Özyurt Bu kişi benim

Z. Buldan Bu kişi benim

Yayımlanma Tarihi 1 Ağustos 2012
Gönderilme Tarihi 11 Ağustos 2015
Yayımlandığı Sayı Yıl 2012 Cilt: 26 Sayı: 2

Kaynak Göster

Vancouver Mıcılı S, Ergür B, Özoğul C, Sarıoğlu S, Bağrıyanık A, Tuğyan K, Pekçetin Ç, Sönmez Ü, Tekmen İ, Erbil G, Akdoğan GG, Özyurt D, Buldan Z. Deneysel Hipertansiyon ve Diyabet Modeli Oluşturulan Sıçanlarda Böbreğin İmmunohistokimyasal Olarak İncelenmesi,. DEU Tıp Derg. 2012;26(2):91-101.