Deneysel Diyabetik Nefropatide Patomorfoloji ve Apoptozis

Yıl 2020, , 29 - 35, 25.06.2020

Nihat Yumuşak

https://doi.org/10.31196/huvfd.686659

Öz

Bu çalışmada diyabetik nefropatiye bağlı oluşan böbrek hasarında histopatolojik ve apoptotik bulguların değerlendirilmesi amaçlandı. Çalışmada 16 rat rastgele olarak kontrol (n=8) ve üç gün arayla iki kez streptozisinle (60 mg/kg, i.p) uyarılmış diyabet (n=8) olmak üzere iki gruba ayrıldılar. Son uygulamayı takip eden 90. günde ratlar uyutularak böbrekleri patolojik incelemeler amacıyla alındı. Dokulara histopatolojik olarak hematoksilen-eozin ve immunohistokimyasal olarak kaspas-3, kaspas-8, kaspas-9 ve TUNEL işaretlemeleri yapıldı. Histopatolojik olarak, tubullerde dilatasyon, atrofi, dejenerasyon, nekroz, glomeruluslarda ise hipertrofi ve vasküler değişikler görüldü. İntersitisyel alanlarda ise yer yer peritubuler, perivasküler ve periglomeruler fibrozis ve inflamasyonlar gözlendi. İmmunohistokimyasal olarak, kaspas-3’ün birçok tubulde pozitif olduğu ayrıca glomerullerde ve intersitisyumda tek tük pozitif hücre ile karşılaşıldı. Kaspas-8 ve kaspas-9 antikorlarının ise birçok tubulde reaktif oldukları belirlendi. TUNEL boyamalarında ise yaygın pozitiflik tubulerde, yer yer intersitisyumda ve glomeruluslarda belirlenmiştir. Sonuç olarak, diyabete bağlı oluşan nefropatide bütün böbrek dokusunda hasarın şekillendiği belirlenmiştir.

Anahtar Kelimeler

Diyabetik nefropati, patomorfoloji, apoptozis

Kaynakça

• Dereli D, Özbal EY, Akyurt M, Günal Z. 1999: Diyabetik nefropati etyopatogenezine güncel bir bakış. J SSK Tepecik Hosp Turkey, 9 (2-3): 66-71.
• Duran-Salgado MB, Rubio-Guerra AF. 2014: Diabetic nephropathy and inflammation, World Journal of Diabetes, 5(3):393-398.
• Estacio RO, Jeffers BW, Gifford N, Schrier RW. 2000: Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care, 23: 54-64.
• Fioretto P, Steffes MW, Sutherland DER, Goetz FC, Mauer M. 1998: Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med, 339:69-75.
• Fioretto P, Vestra MD, Saller A, Mauer M. 2000: Renal structure in type 2 diabetic patients with microalbuminuria. In: Mogensen CE (ed). The Kidney and Hypertension in Diabetes Mellitus. 5th ed. Norwell: Kluwer Academic Publishers, 225-236.
• Fiorina P, Venturini M, Folli F, Losio C, Maffi P, et al.2005: Natural history of kidney graft survival, hypertrophy, and vascular function in end-stage renal disease type 1 diabetic kidney-transplanted patients: beneficial impact of pancreas and successful islet cotransplantation .Diabetes Care, 28 (6):1303-1310.
• Friedman EA. 1996: Renal syndromes in diabetes. Endocrinol Metab Clin North Am, 25:293-24.
• Jones RK, Hamton D, O’Sullivan DJ, et al. 2013: Diabetes and renal disease. Clin Med, 13:460-464.
• Krolewski AS, Warram JH, Freire MB. 1996: Epidemiology of late diabetic complications. A basis for the development and evaluation of preventive programs. Endocrinol Metab Clin North Am, 25:217-242.
• Kumar D, Zimpelmann J, Robertson S, Burns KD. 2004: Tubular and interstitial cell apoptosis in the streptozotocin-diabetic rat kidney. Nephron Exp Nephrol, 96: 77-88.
• Locatelli F, Pozzoni P, Del Vecchio L. 2004: Renal replacement therapy in patients with diabetes and end-stage renal disease. J Am Soc Nephrol, 1:25-29.
• Mauer SM, Chavers BM, Steffes MW. 1990: Should there be expanded role for kidney biopsy in the management of patients with Type 1 diabetes? Am J Kidney Dis, 16:96-100.
• Nadir I, Topçu S, İçağasıoğlu S, Nilüfer Yıldırım N. 2003: Tip II Diabetes Mellitusta Nefropati Gelişiminde Risk Faktörleri. Van Tıp Dergisi: 10 (3):65-68
• Njolstad PR, Sagen JV, Bjorkhaug L, Odili S, Shehadeh N, Bakry D, Sarici, S. U., Alpay, F., Molnes, J., Molven, A., Sovik, O. and Matschinsky, F. M. (2003). Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway. Diabetes. 52(11):2854-60.
• Ortiz A, Ziyadeh FN, Neilson EG. 1997: Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Investig Med, 45: 50-56.
• Ozougwu JC, Obimba KC, Belonwu CD, Unakalamba CB. (2013): The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. J Physiol Pathophysiol, . 4(4): 46-57
• Parving HH, Ostorby R, Anderson PW, Hsuoh WA. 1996: Diabetic nephropathy. In: Brenner BM (ed). The Kidney. 5th ed. Philadelphia: WB Saunders Company, 1864-1892.
• Phillips AO, Steadman R. 2002: Diabetic nephropathy: The central role of renal proximal tubular cells in tubulointerstitial injury. Histol Histopathol, 17:247-252.
• Sarnak MJ, Levey AS, Schoolwerth AC, et al. 2003: American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research,Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease. Hypertension, 42:1050-1065.
• Strippoli GF, Di Paolo S, Cincione R, et al. 2003: Clinical and therapeutic aspects of diabetic nephropathy. J Nephrol,16:487-499.
• Tuncdemir M, Ozturk M. 2008: The effects of ACE inhibitor and angiotensin receptor blocker on clusterin and apoptosis in the kidney tissue of streptozotocin-diabetic rats. J Mol Histol, 39: 605-616.
• Tunçdemir M, Mirzataş EB, Uzun H. 2018: Renoprotective potential of quercetin in experimental diabetic nephropathy: assesing antiapoptotic and antioxidant effects. Arch Clin Exp Med, 3(3):179-185.
• Van Dijk C, Beri T. 2004: Pathogenesis of diabetic nephropathy. Rev Endocr Metab Disord, 5:237-248.
• Wang PH, Chahners TC. 1993: Metaanalysis of effects of intensive blood-glucose control on the late complications of type 1 diabetes. Lancet, 341:1306-1309.
• Warram JH, Gearin G, Laffel L, Krolewski AS. 1996: Effect of duration of Type 1 diabetes on the prevelance of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio. J Am Soc Nephrol, 7:930-937.
• Warram JH, Scott LJ, Hana LS, et al. 2000: Progression of microalbuminuria to proteinuria in Type 1 diabetes: Non linear relationship with hyperglycemia. Diabetes, 49:94-100.
• Wolf G. 2004: New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathology. Eur J Clin Invest, 34:785-796.
• World Health Organization, (2016): Global Report on Diabetes. Geneva: World Health Organization.
• Yaman Y, Kömüroğlu AU. 2018: Deneysel Diyabetik Ratlarda Ardıç (Juniperus communis L.) Yağının Nefropati Üzerine Etkileri. Harran Üniv Vet Fak Derg, 7 (2): 192-199
• Zhang G, Khanna P, Chan LL, et al. 1997: Diabetes-induced apoptosis in rat kidney. Biochem Mol Med, 61: 58-62.