Yenidoğan Streptozotosin Diyabet Modelinde Pankreatik Beta Hücre Rejenerasyonunu Kontrol Eden Genlerin Ekspresyonu

Yıl 2007, Cilt: 38 Sayı: 4, 127 - 138, 20.07.2014

Melek Öztürk Fatma Kaya Dağıstanlı

Öz

Bu çalışmanın amacı, yenidoğan streptozotosin (yd-STZ) diyabet modelinde, erken dönemlerde beta hücre rejenerasyonunu takip etmek amacıyla, insülin, pankreatik duedonal homeobox gen-1 (pdx-1) ve sinaptofisin gen ekspresyonlarını hem adacık içi hem de adacık dışı hücrelerdeki dağılımlarını tespit etmektir. Ayrıca STZ uygulaması ile bozulan adacık düzeninin yeniden yapılanmasında, endokrin hücrelerin rolünü araştırmaktır. Çalışmada, her birinde 7 adet Wistar albino yenidoğan sıçanlardan oluşan 8 grup oluşturuldu. 4 gruba doğumun 2. günü 100 mg/kg tek doz STZ (yd2-STZ) uygulaması yapıldı ve gruplar sırasıyla doğumun 3., 5., 7. ve 10. günlerinde sağlıklı kontrol grupları ile birlikte dekapite edildiler. Alınan pankreas dokuları % 10’luk formolde tespit edilerek parafine gömüldü. Doku kesitlerine insülin probu kullanılarak in situ hibridizasyon yöntemi, ayrıca insü- lin, glukagon, somatostatin, sinaptofisin, pdx-1 antikorları kullanılarak immünohistokimyasal boyama yöntemi uygulandı. STZ uygulanan gruplarda kontrol gruplarına göre adacıkların küçüldüğü, Yd2- STZ diyabetik gruplarda insülin mRNA sinyallerini içeren hücrelerin kapladığı alanın, insülin immün pozitif hücrelerin kapladığı alandan daha az olduğu görüldü. Yd2-STZ grupla- rında adacık içerisindeki immün pozitif pdx-1 hücrelerinin kontrol gruplara göre azaldığı ayrıca tüm deney gruplarında adacıklardaki tüm endokrin hücrelerin sinaptofisin ekspresyonu yaptıkları tespit edildi. STZ uygulanan gruplarda ekzokrin doku ve kanal epiteli içerisinde çok sayıda sinaptofisin immün pozitif hücrelere rastlandı. yd2-STZ modelinde, STZ’nin neden olduğu beta hücre hasarının en fazla görüldüğü günün yd-2 STZ 5 günlük grup olduğu ve 5. günden başlayarak 7 ila 10. günler arasında hızlı bir rejenerasyonun meydana geldiği, sinaptofisin ve pdx-1’in birlikte, olası öncül hücrelerin endokrin hücreye dönüşümünü tespit etmek için iyi birer belirteç olacakları sonucuna varıldı.

Anahtar Kelimeler

Yenidoğan STZ diyabet modeli, β hücre rejenerasyonu, pdx-1, in situ hibridizasyon, sinaptofisin, streptozotosin

Kaynakça

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