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Kronik Puromisin Aminonükleozid (PAN) Nefrozda Renal Fonksiyon, Böbrek Cisimciği Ultrastrüktürü ve Slit Por Sayısı Arasındaki ilişkiler

Relationship of Renal Function, Glomerular Ultrastructure and Slit Pore Count in Chronic Puromycin Aminonucleoside Nephrosis

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2007

Key Words:

Keywords (Original Language):

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Abstract (2. Language): 
Background and Design: In order to create massive proteinuria, puromycin-amin o nucleoside (PAN) is one of the most used models. Podocyte injury causes proteinuria. PAN rats' glomeruli show alterations like minimal change disease in humans, but the mechanism of PAN is not yet understood in total. We aimed to evaluate and show the relationship of renal function and the changes of the ultrastructu-re of the glomeruli, including the number of slit pores in puromycin-aminonucleoside induced chronic nephrosis. Results: 1.67 mg/100 g bodyweight puromycin-aminonucleoside was given subcutaneously to Wistar rats for 12 weeks (the first three weeks, one injection per week; and then, one injection every other week). In the control animals proteinuria was 4.83±3 mg/24 hours and increased up to 247.51*90 mg/24 hours, a fifty fold. Serum albumin in control animals was 3.23+0.1 g/dL and decreased to 2.35+0.38 g/dL, creatinine clearence decreased from 0.55±0.8 mL/min to 0.29+0.1 mL/min. The mean bodyweight increased from 100+8.94 g to 210±24,49 g in the chronic nephrosis animals. Foot processes were fused or retracted. The glomerular basement membrane IGBM) showed elongeted podocyte spikes, especially the perimesangial parts of the GBM foot processes were totally lost and denuded basement membrane could be observed. With help of light microscopy, we observed semiquantitatively significant mesangial matrix expansion in the chronic group animals. Within the expanded mesangial matrix we could see apoptoic mesangial cells, interstitial collagen and frequently macrophages. Endothelial cells also showed apoptoic charecteristics. Evaluating morphometrically 10 urn of the GBM, slit pore count decreased from 32.68±0.62 in controls to 4.87-1.45 in the chronic rats. In the rats with lesser proteinuria, hypertrophic, ultrastructurally rich and sometimes two nucleolus containing podocytes were observed. GBM was focally thickened, invagination into the foot processes and synechias were found. In rats with higher proteinuria, podocytes had pseudocystic degeneration, more thinning elongations and thinning of the basement membranes. Conclusion: We conclude that in rats with chronic puromycin-aminonucleoside nephrosis podocytes degenerate. Slit pore counts decrease and foot processes were lost. Denudation and thinning of the GBM was observed and expansion of the mesangial matrix could be seen. Within the matrix interstitial collagen, macrophages, mesangial and endothelial cell apoptosis established with progressing renal failure and induced the nephrotic syndrome.
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Abstract (Original Language): 
Puromisin aminonükleozid (PAN) masif proteinüri ile seyreden podosit yaralanmasının bir modeli olarak yaygın bir şekilde kullanılmakladır. PAN nefrozlu sıçan glomerüllerinde, minimal değişikliklere sahip insan nefrotik sendromundakilere benzeyen histolojik değişiklikler gösterilmiş, fakat PAN'ın etkisinin tam mekanizması tamamı ile anlaşılamamıştır. Biz de sıçanlarda deneysel olarak oluşturduğumuz kronik PAN nefrozda renal fonksiyon, böbrek cisimciği ultrastrüktürü ve süt por sayısı arasındaki ilişkiyi değerlendirmeyi amaçladık. 1.67 mg/10 0 g PAN subkütanö; olarak 12 hafta süre ile uygulandı. Deney gruplarında proteinüri değeri kontrolde 4.83±3 mg/24 saat iken, kronik nefroz grupta 50 kat artarak 247.5±90 mg/24 saate yükseldi. Bu gruplarda zikredildikleri sıra ile serum albümin ortalaması 3.23+0.1 g/dL'den 2.35+0.38 g/dL'ye, kreatinin klirensi ortalaması ise 0.55±0.8 mL/ dak'dan 0.29+0.1 mL/dak'ya azalmıştı. Hayvanların ortalama ağırlıkları ise kronik grupta fazlaca artarak 100+ 8.94'ten 210+24.49 g'a (kronik grup) yükselmişti. Kronik grupta podosit ayakçıklan kaynaşma/çekilmeleri neticesi glomerüier bazal membran (GBM) üzerinde fazlaca uzamış podosit çıkıntıları, özellikle perimezangiyal GBM bölgelerinde podosit ayakçıklarının tamamıyla kaybolduğu soyulmuş GBM bölgeleri gözlendi. Işık mikroskopuyla yapılan semikantitatif çalışmada da, kronik grupta fazlaca mezangiyal matriks artışı gözledik. Artmış mezangiyal matriks içinde apoptotik özellikler gösteren mezangiyal hücrelere, interstisyel kolajene ve makrofajlara sıklıkla rastlandı. Endotel hücrelerinde de sıklıkla apoptotik görüntüler gözlendi. Morfometrİk çalışmada da 10 pm uzunluğundaki GBM sahasında slit por sayısı ortalaması 32.68±0.62'den (kontrol), 4.87±1.45 (kronik grup) azalmıştı. Kronik grubun daha düşük proteinüri gösteren sıçanlarında hipertrofik, ultrastrüktürden zengin ve yer yer çift nüve ihtiva eden podo-sitler gözlendi. Bu hayvanlarda GBM'de fokal kalınlaşmalar, invaginasyonlar (podosit ayakçığına doğru) synechia'lara rastlandı. Yüksek proteinüri gösteren sıçanlarda podositlerde psödokistik dejenerasyon, fazlaca incelme, uzamalar ve GBM'de de fazlaca incelmeler gözlendi. Bulgularımız kronik PAN uygulamasının bozulan renal fonksiyon ile ilişkili giderek artan podosit dejenerasyonu, slit por azalması, podosit ayakçıklarının yok olması (GBM çıplaklaşması), GBM incelmesi, mezangiyumda matriks artışı, interstisyel kolajenin belirmesi, makrofajların görülmesi ve mezangiyal, endotel hücre apoptozisi ile birlikte seyreden bir nekrotik sendromu indüklediğini düşündürmektedir.
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