Farklı doz ve uygulama zamanlarında Streptozotocin’in sıçanların pankreatik ada hücreleri üzerine apoptotik etkileri

Ada hücrelerinin apoptotik hücre ölümü ile kaybedilmesi hiperglisemi ve diyabet gibi deneysel hayvan modellerinin patogenezinde merkezi bir yol oynar. Streptozotocin (STZ) pankreatik  hücrelerinin tahrip edilmesi yolu ile hayvanlarda diyabetin uyarılmasi için sıklıkla tercih edilmektedir. Bu çalışmanın amacı farklı doz ve uygulama zamanlarında STZ’nin pankreatik ada hücreleri üzerine olan etkilerinin arastırılmasıdır. Bu amaçla sitrat tamponu (0.01 M, pH: 4.5) uygulanan, 40 mg/kg STZ enjekte edildikten 5 saat sonra sakrifiye edilen, 60 mg/kg STZ enjekte edildikten 6 saat sonra sakrifiye edilen ve 75 mg/kg STZ enjekte edildikten 4 saat sonra sakrifiye edilen hayvanlar olmak üzere 4 farklı deney grubu oluşturuldu. Apoptotik hücreler TUNEL işaretleme tekniği ve hücrelerin morfolojik özellikleri göz önüne alınarak belirlenirken, insulin üreten β hücreleri immünohistokimya tekniği kullanılarak gösterildi. Sonuç olarak, 40 ve 75 mg/kg STZ uygulanan sıçanların kan Gezginci-Oktayoglu/ IUFS Journal of Biology 2011, 70(2): 43-51 glukoz miktarında ve apoptotik ada hücre sayısında bir artış gözlenirken, tüm gruplarda ada ve β hücre alanlarında azalma olduğu tespit edildi. Bu bulgular, 40 ve 75 mg/kg STZ enjeksiyonunun sırasıyla 5 ve 4. saatin sonunda erişkin sıçanların ada hücrelerinde apoptozu uyararak hiperglisemiye neden olduğunu göstermektedir.

The apoptotic effects of Streptozotocin in different dose and administration time on pancreatic islet cells of rats

The loss of islet cells by apoptotic cell death plays a central role in the pathogenesis of experimental animal models such as hyperglycemia and diabetes. Streptozotocin (STZ) is widely used for the induction of diabetes in animals by destruction of pancreatic  cells. The aim of the present study is to determine the effects of different dose and administration time of STZ on pancreatic islet cells. With this aim, four different experimental groups consist of the animals treated with citrate buffer (0.01 M, pH: 4.5) only, the animals sacrificed after 5 hours of the 40 mg/kg STZ injection, the animals sacrificed after 6 hours of the 60 mg/kg STZ injection, and the animals sacrificed after 4 hours of the 75mg/kg STZ injection were composed. While the apoptotic cells were observed by TUNEL staining method and according to morphologic criteria of the cells, insulin synthesized cells were shown by immunohistochemical technique. As the result it was determined an increase in blood glucose levels and apoptotic islet cells in 40 and 75 mg/kg STZ-injected rats while islet and beta cell areas were decreased in all groups. These results indicate that 40 and 75 mg/kg STZ injection at the end of 5 and 4 hours, respectively, causes hyperglycemia by triggering apoptosis in islet cells of adult rats. Keywords: Apoptosis, hyperglycemia, islet cell, rat, streptozotocin.
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